Catharine Winstanley

Prospective Graduate Students / Postdocs

This faculty member is currently not actively recruiting graduate students or Postdoctoral Fellows, but might consider co-supervision together with another faculty member.


Research Interests

Behavioural neuroscience
decision making
Gambling disorder
Mental Health and Society
Neuronal Systems
Computational neuroscience
Traumatic Brain Injury

Relevant Thesis-Based Degree Programs

Research Options

I am available and interested in collaborations (e.g. clusters, grants).
I am interested in working with undergraduate students on research projects.

Research Methodology

Cognitive behavioural testing in rodents
Behavioural pharmacology
Drug self-administration in rats

Great Supervisor Week Mentions

Each year graduate students are encouraged to give kudos to their supervisors through social media and our website as part of #GreatSupervisorWeek. Below are students who mentioned this supervisor since the initiative was started in 2017.


Need to point out how inspirational and supportive @cawinstanley has been! #GreatSupervisor #UBC



Graduate Student Supervision

Doctoral Student Supervision

Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.

Towards a better understanding of the bidirectional relationship between decision-making and addiction vulnerability (2024)

Impaired decision-making is recognized as a diagnostic criterion for many different psychiatric disorders including gambling disorder and substance use disorders. Habit formation and cue responsivity are known to play a role in driving these disorders, but less is known as to if and how decision-making is differentially altered by different classes of abused drugs. The impact of biological sex is also vastly understudied in such contexts. To gain further understanding on the bi-directional relationship between decision-making impairments and addiction, we combined the well-established rat gambling task with volitional drug self-administration in both male and female rats. In one aim, I sought to pharmacologically manipulate habit formation via the systemic administration of a histone deacetylation inhibitor. I found that inhibiting histone deacetylation resulted in increased risky choice during acquisition of our rat gambling task, while also altering how rats were learning from task outcomes. In another aim, I sought to further characterize the effect of cues on decision-making by allowing rats to choose between the cued and uncued rat gambling task on a trial-by-trial basis. I found that cues had negative effects on cognition, despite being preferred to their absence. I then paired this task with cocaine self-administration to investigate the bi-directional effects of gambling and cocaine-taking. I found evidence for cocaine-induced motivational deficits on subsequent gambling sessions. In my final aim, I sought to determine whether fentanyl could induce the same decision-making impairments that we had previously observed in response to cocaine. I found that while acute fentanyl self-administration did not impact cognition, fentanyl withdrawal did have long-lasting negative effects on decision-making.

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Cognitive and neural underpinnings of the interaction between reward-paired cues, risky choice, and cognitive flexibility (2023)

Deficits in cost/benefit decision making are a critical risk factor for substance use disorder and behavioural addictions such as gambling disorder. Reward-concurrent cues may mediate this relationship, as such stimuli enhance risk preference and can potentiate cocaine intake in rats. To investigate the influence of cues on brain functioning and cost/benefit decision making, we utilize the rat Gambling Task. This task was designed such that maximal reward is attained by avoiding the high-risk, high-reward options and instead favouring the options associated with lower per-trial gains, as they feature less frequent and shorter time-out penalties. Adding reward-paired audiovisual cues to the task leads to greater risky choice on average. As inflexible pursuit of rewards is a critical component of drug and behavioural addictions, I tested whether these cues can also induce inflexibility in choice patterns. Results showed that win-paired cues but not loss-paired or randomly occurring cues drive risky choice as well as inflexibility in responding following shifts in reinforcer value. I also investigated potential neurobiological mechanisms of the impact of cues on decision making. I showed that altering serotonergic signaling in the lateral OFC can both ameliorate cue-induced risky choice and restore sensitivity to reinforcer devaluation. Furthermore, I showed that altering lateral OFC activity differentially affects choice patterns during early task learning on the uncued versus cued rGT, further demonstrating that OFC output is substantially impacted by the inclusion of cues on the task. I also showed that dopamine activity in the dorsal striatum is involved in the development and performance of choice patterns on the cued rGT, at least in females; inhibiting dopamine pathways projecting to the dorsal striatum resulted in an initial increase in risky choice followed by a subsequent long-term improvement in decision making. Thus, the role of dopamine in guiding choice towards versus away from risky options on the cued rGT shifts over time. Overall, these results shed light on the interaction between reward-paired cues, risky choice, and inflexible responding, thus providing insight into cue-induced compulsive risky behaviours that underlie both substance use disorder and gambling disorder.

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Probing the role of dopamine at the intersection of addiction, decision making, and sex (2021)

Addiction is an escalating, compulsive, and relapsing psychiatric disease that affects millions worldwide and exacts immense socioeconomic cost. As for potential pharmacotherapeutic targets, the dopamine system is of most interest, but it is unclear as to whether increasing or decreasing dopamine is the best approach. There is consensus that the cues associated with cocaine use and gambling (e.g., a crack pipe or flashing casino lights) are critical in driving disordered behaviour. It is also clear that the responsivity to drug and gambling cues is governed by dopamine and that there is considerable comorbidity between cocaine use and gambling disorder. Biological sex also plays a critical role in addiction but is confounded by the socioeconomic construct of gender in human studies, necessitating animal models. In the following thesis, we preclinically modeled the complex intersection of cocaine use and gambling-like behaviour by combining operant cocaine self-administration with the cued rat gambling task. While female and male rats gambled and took cocaine, we used chemogenetics to bidirectionally modulate the dopaminergic neurons projecting from the ventral tegmental area. We showed that chemogenetic inhibition of dopamine neurons decreased numerous addiction-like behaviours (e.g., risk-taking, impulsivity) in males, but surprisingly increased risk-taking in females. In both sexes, stimulation of the dopamine system had generally deleterious effects. Both inhibition and stimulation caused females and males to take more cocaine, but paradoxically prevented the increased risk-taking that results from cocaine self-administration. Drawing on the reward deficiency and incentive sensitization theories of addiction, this thesis furthermore proposes a biobehavioural framework through which the present findings may be understood.

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Investigating the neurobiological underpinnings and structural characteristics which contribute to biased decision making (2019)

Gambling disorder (GD) and other forms of behavioural and substance addictions are characterized by deficits in decision making and impulsivity. Animal models of behaviour allow researchers to study specific components and features of biased decision making and elucidate the neural circuitry that underpins these biases. Our laboratory has developed several animal models which each examine a specific subfacet of decision making thought to contribute to GD. The rat Gambling Task examines risky decision making by posing a choice between small, safe rewards and larger but more risky options. The rat Betting Task examines a specific choice bias termed the “escalation of commitment” bias, in which humans show an increasing aversion to uncertain wagers as the amount at stake goes up. In order to examine the effect of cues on choice behaviour, we developed the Cued rat Gambling Task, which offers the same choice options as those on the rat Gambling Task, but pairs wins on the risky options with salient cues. The presence of salient environmental stimuli can influence choice behaviour, and may make important contributions to the maintenance and severity of GD.As described in this dissertation, work with these tasks has clarified the environmental, pharmacological and regional contributions to GD-like decision making. The development of the Cued rat Gambling Task demonstrated that the addition of salient cues is sufficient to drive a riskier, more disadvantageous choice preference than that demonstrated on the uncued rat Gambling Task. Disrupting orbitofrontal cortex function while the animal is learning the Cued rat Gambling Task promotes the development of a more optimal choice strategy, perhaps due to the region’s roles in cognitive flexibility and subjective valuation. Choice biases on the rat Betting Task are also ameliorated by inactivation of the orbitofrontal cortex, but not inactivation of other prefrontal regions. Furthermore, the nucleus accumbens core, but not shell, may guide the development of a risk-averse choice strategy on the rat Gambling Task. In sum, the work in this dissertation clarifies the motivational role of cues in gambling and other disorders of addiction, and elucidates the neural circuitry that underpins choice biases.

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Investigating the neurobiology regulating cognitive effort allocation using a rodent model of cost/benefit decision making (2018)

Choosing adaptively among candidate actions requires a cost-benefit analysis, inwhich potential rewards are considered against the costs required to obtain them.One cost frequently encountered by humans is the cost of cognitive effort, inwhich executive processes spanning attention, working memory, reasoning, andthe like are taxed. This form of effort is in contrast to the physical effort costs thathave generally been the focus of the cost/benefit decision-making literature. Thisthesis reviews the currently available literature investigating the brain regions andneurotransmitter systems guiding these respective forms of decision making, andthen carries out a set of experiments to further characterize the neurobiologyguiding cognitive effort allocation. These experiments utilize an animal model ofdecision making known as the rodent Cognitive Effort Task (rCET), in whichsubjects decide whether to exert more attention in pursuit of larger rewards, or toobtain smaller reward for comparatively less attentional demand. In experiment1, I use chemogenetics to downregulate cholinergic neurons of the basalforebrain as rats perform the rCET, to determine whether this neuronalpopulation is responsible for the previously ascribed role of acetylcholine inregulating decision making with cognitive effort costs. Experiments 2 and 3 usestandard inactivation techniques to investigate striatal and orbitofrontal cortexcontributions to this form of decision making, and Experiment 4 uses adisconnection procedure to assess whether BLA- ACC signaling regulates willingness to apply cognitive effort. Collectively, the current findings complementexisting work in the domain of physical effort allocation, and support the notionthat these two forms of effort-based decision making are mediated by distinct,albeit overlapping circuitries. While this work fundamentally contributes to anunderstanding of how organisms navigate their environment, it also has practicalutility. Indeed, work with the rCET and related cognitive effort paradigms mayhelp identify behavioural or pharmacological therapies that can boost cognitivewillingness. Alternatively, information gained may shed light on the aberrantprocesses underlying a blunted desire to achieve lucrative outcomes, asobserved in disorders like depression, schizophrenia, and Parkinson’s Disease.

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Investigating the influence of risky decision making on dopaminergic reward mechanisms (2017)

Addiction is a chronic relapsing psychiatric disorder affecting millions worldwide. Despite years of research investigating the etiology and phenomenology of substance abuse, there is no cure. Determining factors which promote the addictive phenotype may help to discover new therapeutics. Several clinical studies have shown addicts demonstrate poor cost/benefit decision making as measured by validated tasks such as the Iowa Gambling Task (IGT), a cognitive deficit maintained during periods of abstinence and associated with relapse risk. However, it is unclear whether disadvantageous choice precedes or is the consequence of drug abuse. Furthermore, dopaminergic signalling, actively recruited by drugs of abuse, has also been implicated in decision-making biases, and may contribute to choice deficits after drug exposure. The experiments here explored the role of disadvantageous choice in addiction susceptibility using rodent analogues of the IGT, the rat gambling task (rGT) and cued rat gambling task (crGT). These paradigms require the animal to choose between four different nose poke options which are associated with sugar wins, probabilities of winning, and timeouts. The crGT also includes salient reward-paired cues to enhance risky decision making. The first two experiments assessed whether baseline risk-preference on the rGT and crGT affected drug seeking as measured by cocaine self-administration, and whether drug exposure affected task performance. The third study examined the influence of task experience on the locomotor response to cocaine and responding for conditioned reinforcement, two dopamine-dependent behavioural assays associated with addiction risk. Basal and cocaine-induced nucleus accumbens dopamine release was also assessed using microdialysis after task training. The final study used chemogenetics to reduce nucleus accumbens dopamine to investigate the role of dopaminergic tone in choice biases. Our results show poor decision making precedes drug exposure, and is uniquely susceptible to drug-induced cognitive deficits. crGT rats showed greater drug seeking and sensitivity to cocaine-induced choice impairments, a phenotype linked to basal accumbal dopamine efflux. Finally, by reducing accumbens dopamine, animals showed marked reductions in risky choice. These data support the conclusion that poor decision making may serve as a cognitive endophenotype for addiction via aberrant dopaminergic signaling within the mesostriatal network.

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Neurobiological and behavioural effects of chronic administration of the D2/3 agonist ropinirole in relation to iatrogenic gambling disorder (2017)

Neurobiological changes in Parkinson’s Disease (PD) involve dramatic loss of dopamine neurons in the substantia nigra (SNc) and terminals in the dorsal striatum. L-DOPA, first line treatment for PD, can produce debilitating side-effects like dyskinesia over time. Preferential dopamine D2/3 agonists like ropinirole, are used to treat PD, but these newer drugs can lead to impulse control disorders (ICDs) and gambling disorder in a significant minority of patients. The mechanism mitigating dopamine replacement therapy (DRT)-induced ICDs, or whether premorbid behavioural tendencies are a risk factor are unknown. We show that chronic ropinirole increases preference for uncertainty on the rodent Betting task (rBT), regardless of animals’ baseline preference for the safe or uncertain option. Comparatively, ropinirole had subtle effects on choice of a cued version of the rat Gambling task (rGT), while increasing impulsivity, suggesting different neural mechanisms in performance of these tasks. GSK3ß has been involved in disorders of impulsivity suggesting a potential intracellular mechanism for DRT-ICDs. However, chronic administration of SB 216763, a GSK3ß inhibitor, did not attenuate gambling-like behaviours following ropinirole, but also did not reliably decrease GSK3ß levels, such that we were unable to unequivocally determine its role in ropinirole-induced preference for uncertainty. The “overdose” hypothesis, in which DRTs would replenish dopamine stores in the deteriorated dorsal striatum and improve movement, but overwhelm the mostly spared mesolimbic reward system, was suggested to explain DRT-ICDs in PD. However, newer studies suggest a potential involvement for the nigrostriatal, rather than mesolimbic, pathway in gambling disorders. We therefore manipulated the nigrostriatal pathway using designer receptors exclusively activated by designer drugs (DREADDs). Activation of dopamine neurons in the SNc increased preference for uncertainty on the rBT in wager-sensitive rats, partially mimicking the effect of ropinirole, while inhibition of these neurons had no effect on the increase in preference for uncertainty caused by ropinirole. These studies suggest a potential role for activation of the nigrostriatal pathway in DRT-ICDs. They also suggest that ICDs result from DRT alone, rather than from an interaction between medication and basal risk preference, or change in dopamine function caused by the diseases for which they are prescribed.

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Elucidating the neurobiology of problem gambling using a novel rodent slot machine task (2016)

Gambling is an enjoyable and innocuous past-time for many, but for some it can become a maladaptive compulsion akin to drug or alcohol addiction. Despite increasing recognition that the phenomenological process underlying both substance and behavioural addictions may be similar, treatment options for problem gambling remain limited, and of questionable efficacy. Animal models offer an invaluable opportunity to not only study the underlying neurobiology of disorders such as gambling, but may also facilitate the development of novel pharmacotherapies. To that end we have developed a rodent slot machine task (rSMT) that suggests rats share key behavioural features with human gamblers. The dopamine D₂-like receptor family is critically involved in modulating animals’ performance on the rSMT. Specifically, the D₄ receptor appears to contribute to animals’ attributions of salience to game-related stimuli. D₄ receptors are principally located within prefrontal cortical regions and consequently represent an intriguing target for modulating higher order cognitive processes. In addition to systemic pharmacology, we have demonstrated that disruption of neural regions that are relatively rich in D₄ receptors, such as the anterior cingulate and insular cortex, impact animals’ ability to accurately respond to reward-related stimuli on the rSMT; further emphasising a role for these receptors in gambling-related decision making.Additionally, we have used the rSMT to try and model iatrogenic gambling observed in patients with Parkinson’s disease (PD). This form of compulsive gambling arises de-novo in a small but significant sub-set of patients following adjunctive therapy with D₂-like agonists. Chronic administration of a D₂/₃ receptor agonist galvanized performance on the rSMT, a finding that could be considered translationally analogous to the compulsive play exhibited by some PD patients. These alterations in performance were accompanied by an increase in the transcription factor pCREB in the nucleus accumbens. Administration of the β-adrenoreceptor blocker propranolol, which putatively attenuates this increase in pCREB, ameliorates the compulsive-like task engagement. Ultimately, gambling is a heterogeneous disorder that is unlikely to have a single underlying aetiology. However, these data indicate that aberrant dopaminergic signalling within the D2-like receptor family may underlie at least some of the cognitive perturbations observed in problem gambling.

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Elucidating the neurobiology and individual differences of cost/benefit decision making using a novel rat task of cognitive effort (2014)

Amotivational states and insufficient recruitment of mental effort have been observed in a variety of clinical populations, including depression, traumatic brain injury, post-traumatic stress disorder, and attention-deficit/hyperactivity disorder. Previous animal models of effort-based decision making have utilized physical costs whereas human studies of effort have been primarily cognitive in nature, and it is unclear whether the two types of effortful decision making are underpinned by the same neurobiological processes. We therefore validated a novel rat Cognitive Effort Task (rCET) based on the five-choice serial reaction-time task, a well-established measure of attention and impulsivity. Within each rCET trial, rats were given the choice between an easy or hard visuospatial discrimination, and successful hard trials were rewarded with double the number of sugar pellets. Similar to previous human studies, stable individual variation in choice behaviour was observed, with “workers” choosing hard trials significantly more than their “slacker” counterparts. We used a variety of pharmacological agents as well as temporary inactivation of select brain regions, and showed that the effects of these manipulations often interacted with animals’ baseline preferences. Amphetamine and caffeine caused workers to “slack off”, whereas slackers “worked harder” under amphetamine but not caffeine. Dopamine antagonism had no discernible effects on animals’ choice, contrary to the physical-effort literature. The cholinergic drug nicotine decreased slackers’ willingness to expend effort, whereas scopolamine more substantially decreased workers’ choice of the high-effort option. Temporary inactivation of the basolateral amygdala caused workers to slack off and slackers to work harder, whereas anterior cingulate and medial prefrontal cortex inactivations caused all animals to slack off. In sum, we have shown for the first time that rats are differentially sensitive to cognitive effort when making decisions, independent of other processes such as impulsivity, and these baseline differences appear to be reflected by differences in underlying neurobiology. Further, we demonstrate that mental and physical effort are in part dissociable, both behaviourally and in terms of neurochemistry and neural circuitry. Such findings could inform our understanding of the neurobiological basis of decision making as well as impairments in effort-based decision making, and may contribute to novel therapeutic interventions.

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Investigating the neurobiological basis of decision-making using a novel rat gambling task (2012)

The Iowa Gambling Task (IGT) is a commonly used clinical test of decision-making. During the IGT, subjects choose between options associated with gains and losses. We have developed a novel rat gambling task (rGT), during which subjects are required to maximize their earnings within a 30 min session. Animals choose between four options, each associated with a different number of sucrose pellets, probability of receiving reward, and the magnitude and possibility of experiencing a punishing time-out period during which reward cannot be earned. Persistent choice of the larger reward options results in greater loss—as these options are associated with more frequent and longer time-out periods—resulting in less reward earned per unit time. Therefore, similar to the IGT, subjects are required to choose from the smaller reward options to maximize long-term gains. Results from Experiment 1 demonstrated that rats learn to choose most often from the best option by incorporating multiple factors into making their decisions. Therefore, the rGT may be a useful tool to study the biological basis of decision-making. Following pharmacological challenges with amphetamine and receptor-specific serotonergic and dopaminergic agents, data from Experiments 1 and 2 demonstrated that both neurotransmitters play important roles in modulating decision-making preferences. Furthermore, results from Experiment 2 suggested that amphetamine’s ability to alter decision-making may not be caused by increased dopamine release. Additionally, animals reared in an enriched environment or in isolation were slower to learn the optimal strategy, but only isolation-reared rats chose more often from the disadvantageous options. Experiment 3 determined that lesions of either orbitofrontal cortex (OFC) or basolateral amygdala (BLA) impaired acquisition of the rGT. However, if these lesions occurred after training on the rGT, only rats with BLA lesions chose disadvantageously. These results indicated that the BLA—but not the OFC—is involved in maintaining an optimal strategy on the rGT, yet both regions are required during task acquisition. Experiment 4 used a contralateral disconnection lesion procedure to determine that the connectivity between the OFC and BLA was important in learning the optimal strategy, as well as updating decision-making preferences following reward devaluation.

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Master's Student Supervision

Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.

Dissociating the role of prefrontal noradrenaline signaling in cost-benefit decision making and impulsive action (2023)

Win-paired stimuli can promote risk taking on experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risky choice on the cued rat gambling task (crGT), a rodent decision making task in which wins are accompanied by salient audiovisual cues. Both compounds also decreased impulsive premature responding. However, the central mechanisms behind noradrenergic regulation of cue-guided risk taking and impulsivity have not yet been elucidated. Areas of the prefrontal cortex such as the lateral orbitofrontal cortex (lOFC) and prelimbic (PrL) subregion of the medial prefrontal cortex receive dense noradrenergic innervation and are highly implicated in risk assessment, action selection and impulse control. I therefore probed the prefrontal substrates of noradrenaline’s influence over gambling-like behaviour by infusing atomoxetine and guanfacine directly into either the lOFC or PrL prior to task performance. Atomoxetine infused into the lOFC improved decision making score in male rats but did not alter decision making in females. Atomoxetine also improved impulse control when infused into the PrL, yet only in risk preferring animals. Contrastingly, intra-PrL guanfacine exacerbated motor impulsivity in all subjects. Our data reveal a double dissociation such that lOFC noradrenaline importantly guides decision making, at least in males, while PrL noradrenaline signaling regulates motor impulsivity. We also show that noradrenergic manipulations differentially influence behaviour depending on baseline risk preference, suggesting that the noradrenaline system may function differently in subjects that are susceptible to the risk-promoting lure of win cues.

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Behavioural effects of D2/3 and D3 agonist drugs: implications for iatrogenic impulse control disorders (2022)

The chronic use of dopamine agonist drugs to treat diseases such as Parkinson’s has been associated with the development of impulse control disorders. It is hypothesized that this mainly occurs through action at D3 receptors thereby inducing sensitization of the mesolimbic dopamine system, increasing impulsivity and risky decision making. Using a preclinical model, I tested the effects of chronic ropinirole, a commonly prescribed D2/3 receptor agonist, on performance on the rodent gambling task in healthy female rats. I subsequently investigated the effect of chronic D3 receptor activation via a selective agonist on rGT performance in male rats. The data I present in this thesis suggests that ropinirole does not have the same risk promoting effects in female rats as it does in males. Additionally, my data challenges the hypothesis that D3 receptors are solely responsible for the increase in risky decision making caused by ropinirole in males.

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Evaluation of a novel treatment for dopamine agonist-induced impulse control disorders for Parkinson's patients (2019)

Selective dopamine D⅔ receptor agonists, such as ropinirole (ROP), effectively treat themotor symptoms of Parkinson’s Disease (PD), and unlike L-dopa, do not cause problematicdyskinesias after prolonged use. Thus, D⅔ agonists can be an attractive alternative to L-dopa forthe long-term management of PD. However, D⅔ agonists induce impulse control and gamblingdisorders in a substantial minority of patients, raising concern over the use of these agents.Adjunctive medications that could be safely administered with D₂/₃ agonists and prevent thedevelopment of such psychiatric side-effects would therefore be highly desirable. GPR52 is aGs-coupled g-protein coupled receptor (GPR) enriched in D2 receptor expressing neurons of thestriatum. Activation of GPR52 has been demonstrated to attenuate behaviours associated withincreased striatal dopamine release without altering basal function. We have previously shownthat ROP increases preference for uncertain outcomes on a rodent test of gambling-like decisionmaking known as the rodent betting task (rBT). This task measures preference for certain versusuncertain rewarding outcomes of equal expected value. Although most rats maintain a constantpreference for the uncertain outcome regardless of the amount at stake, some rats increase theirpreference for guaranteed rewards as the wager-size increases, despite the relative expectedvalue of the two options remaining constant. The choice strategy of these wager-sensitive ratsmay be considered mathematically non-normative, and such irrational decision-making patternshave been linked to the manifestation and severity of problem gambling. The degree of wager sensitivity has been associated with the density of D⅔ receptors in the dorsal striatum. I therefore hypothesized that GPR52 agonists may attenuate the ability of ROP to promote choice ofuncertain outcomes in wager-sensitive rats on the rBT. I tested this hypothesis by administeringGPR52 agonists BD442618 and S111224 in two cohorts of healthy male rats that were also implanted with osmotic pumps, delivering either ROP or saline. The rats performed the rBT for28 days after osmotic pump implantation. A reduction in ROP’s ability to increase preference foruncertainty on the rBT would suggest that GPR52 agonists may be a potential treatment foriatrogenic impulse control and gambling disorders.

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Muscarinic Receptor Contributions to Cost/Benefit Decision-Making on the Rat Gambling Task y (2014)

The cholinergic system, encompassing the muscarinic and nicotinic receptor systems, plays a modulatory role in a variety of executive processes. However, its role in decision making is still unclear. Disorders characterized by disturbed muscarinic receptor functioning, such as schizophrenia, exhibit impaired performance on measures of real-world cost/benefit decision making, but whether this contributes to the choice deficits observed in the disorders is currently unknown. To address muscarinic receptor contributions to such processes, we investigated the effects of the broad-acting muscarinic receptor agonist oxotremorine (0.01, 0.03. 0.1 and antagonist scopolamine (0.01, 0.03, 0.1 on rodent Gambling Task (rGT) performance. Like the clinically administered Iowa Gambling Task (IGT), rodents must evaluate the costs and benefits of four nosepoke options that are each associated with the delivery of a different amount of reward, as well as different probabilities of receiving reward or a punishment time-out in which no reward can be earned. Rats quickly learn to select the advantageous options characterized by smaller rewards with lower penalties, and to avoid the large, high penalty reward options. Although systemic administration of oxotremorine had no effect, the highest dose of scopolamine impaired optimal performance by increasing choice of the option associated with the smallest reward and the lowest risk. This shift in choice is similar to that previously observed following administration of amphetamine, and suggests the drugs induce a hypersensitivity to loss. Given the functional connectivity of muscarinic and dopaminergic systems in the brain, and the antipsychotic-like profile of muscarinic agonists in amphetamine-induced animal models of schizophrenia, we then attempted to attenuate amphetamine’s choice impairments by prior administration of oxotremorine. Amphetamine (1.0 produced its characteristic choice impairments, despite pretreatment with oxotremorine. The results of this study suggest muscarinic receptor blockade can impair cost/benefit decision-making under conditions of risk and uncertainty, and prescribe a novel role to acetylcholine as a modulator of the decision process. Future work is required to pinpoint the mechanism driving amphetamine’s effect on the rGT, as cholinergic signaling through muscarinic receptors does not appear to be involved.

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Salient Win-Paired Cues Mediate Decision Making on a Rodent Gambling Task (2014)

Background:Pathological gambling is a pervasive and destructive behavioral disorder in which individuals lose control over their gambling behavior, leading to severe personal, social and financial consequences. Current animal models of gambling behavior such as the rodent gambling task (rGT) are useful tools with which to evaluate choice behavior. However, they are limited in their insights into gambling behavior in that they mostly model dimensions of economic decision-making, but not the salient cues intrinsic to human gambling paradigms. Here, we developed a task called the cued rGT to examine the potential influence of salient win-associated cues on decision-making. Methods:16 male Long-Evans rats were tested on either the traditional or a cued version of the rGT. Once trained, they were treated with a number of dopaminergic compounds to delineate the role of this neurotransmitter in guiding choice behavior in both cued and uncued tasks.Results:Animals on the cued task showed a more disadvantageous choice preference at baseline than animals on the uncued task. Amphetamine caused a significant increase of a safe, certain option in both versions of the task, a result that is somewhat consistent with past findings. Quinpirole, a D2-like agonist, increased disadvantageous choice in the cued group but not the uncued group. There were no effects of eticlopride, a D₂-like antagonist, or selective D4 drugs on choice performance.Conclusions:Salient win-associated cues are sufficient to drive a shift towards disadvantageous choice preference. This effect appears to be mediated, at least in part, by D2-like receptors. These finding suggest the cued rGT is a valuable model with which to study how salient cues can invigorate maladaptive decision making, an important and understudied component of pathological gambling and substance use disorders.

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With Great Power Comes Great Responsibility: China's Dilemma in Responding to Humanitarian Crises (2014)

The People’s Republic of China has increasingly been asserting its role as a responsible power in international affairs, emphasizing its engagement in and contribution to UN peacekeeping missions and its key role as a veto-yielding Security Council member. This thesis investigates that while China continues to champion a strong conception of state sovereignty in interstate relations, it has signaled a shift from an ideological insistence on non-interference toward a more pragmatic approach to humanitarian crises. This paper demonstrates how after 2005 China has managed to position itself in a ‘grey zone’ of uncertainty, that is to say that China’s dilemma is wanting to appear responsible on the international level but also wanting to adhere to safe principles such as non-interference and sovereignty. Therefore, it is my argument that China will never fully endorse R2P or any alternative norm that will justify foreign intervention in a sovereign state. While China continues to show support for alternative formulas for civilian protection, such as the Brazilian ‘Responsibility while Protecting’ (RwP), as well as develop its own version of R2P, ie. ‘Responsible Protection’ (RP), it is not to turn “words into deeds” but rather to keep up with appearances. China’s current position on responding to humanitarian crises is ambiguous. The principles behind RP represent a very useful conceptual approach to the issue of humanitarian protection, but the probability of implementing them is virtually non-existent. RP indicates that China has been more responsive to external criticisms in recent years, but does not fundamentally help to discern where China stands on responding to humanitarian crises. Because of RP’s tight criteria, China ensures that in practice no intervention can ever fully be justified, while appearing to advance more ‘responsible’ approaches to civilian protection as its great-power status and privileged position as a permanent member of the United Nations Security Council permit it to do so.

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Kindling, drugs and decision-making: an exploration of the effect of anticonvulsant drugs and provoked seizures on a rat Gambling Task (2013)

Impulsivity is a major component of mania in bipolar disorder, and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are also observed in some patients with temporal lobe epilepsy (TLE), in which seizures originate in the amygdala and hippocampal formations, and incidence of pathological gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of bipolar disorder. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioural aspect targeted by these drugs. Patients with damage to the basolateral amygdala (BLA) also show deficits in decision-making, and rats with BLA lesions have shown such deficits in a variety of behavioural tasks. Few studies have looked at the effect of BLA stimulation on risky decision-making. This project first aimed at exploring the effect of the three anticonvulsant drugs currently also used as mood stabilisers- carbamazepine, valproate and lamotrigine- on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). We then investigated the effect of kindling of the BLA on this task, with the aim of antagonizing any behavioural effects with the anticonvulsant drugs. Thirty-two rats in total learned the rGT. Sixteen rats were used in the pharmacology study, and 16 were implanted unilaterally with a bipolar electrode into the BLA and stimulated twice daily until kindling had been established i.e. three class five seizures were observed. Carbamazepine appeared to slow processing speed, decreased premature responses and also blocked the pro-impulsive effect of amphetamine. Kindling increased choice of the small, but immediate reward option P1 and also increased premature responses. However, none of the changes observed were permanent and therefore, we could not assess the effect of carbamazepine on blocking the effect of kindling. Further studies looking at chronic administration of anticonvulsants, and the effect of kindling on acquisition of the rGT, would help us understand the neurobiological mechanisms underlying vulnerability to impairments in decision-making under uncertainty associated with TLE and other psychiatric disorders.

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