Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications

Our willingness to take risks, our ability to wait or the speed with which to make decisions are central features of our personality. However, it is now recognized that impulsive and risk-taking behaviours are not a unitary construct, and different aspects can be both psychologically and neurally dissociated. The range of neurochemicals and brain systems that govern these behaviours is extensive, and this may be a contributing factor to the phenotypic range seen in the human population. However, this variety can also be pathological as extremes in risk-taking and impulsive behaviours are characteristics of many neuropsychiatric and indeed neurodegenerative disorders. This spans obsessive–compulsive disorder, where behaviour becomes ridged and non-spontaneous, to the nonsensical risk-taking seen in gambling and drug taking

Effects of 5-HT2C, 5-HT1A receptor challenges and modafinil on the initiation and persistence of gambling behaviours

Rationale Problematic patterns of gambling are characterised by loss of control and persistent gambling often to recover losses. However, little is known about the mechanisms that mediate initial choices to begin gambling and then continue to gamble in the face of losing outcomes. Objectives These experiments first assessed gambling and loss-chasing performance under different win/lose probabilities in C57Bl/6 mice, and then investigated the effects of antagonism of 5-HT2CR with SB242084, 5-HT1AR agonism with 8-OH-DPAT and modafinil, a putative cognitive enhancer. Results As seen in humans and other species, mice demonstrated the expected patterns of behaviour as the odds for winning were altered increasing gambling and loss-chasing when winning was more likely. SB242084 decreased the likelihood to initially gamble, but had no effects on subsequent gambling choices in the face of repeated losses. In contrast, 8-OH-DPAT had no effects on choosing to gamble in the first place, but once started 8-OH-DPAT increased gambling choices in a dose-sensitive manner. Modafinil effects were different to the serotonergic drugs in both decreasing the propensity to initiate gambling and chase losses. Conclusions We present evidence for dissociable effects of systemic drug administration on different aspects of gambling behaviour. These data extend and reinforce the importance of serotonergic mechanisms in mediating discrete components of gambling behaviour. They further demonstrate the ability of modafinil to reduce gambling behaviour. Our work using a novel mouse paradigm may be of utility in modelling the complex psychological and neurobiological underpinnings of gambling problems, including the analysis of genetic and environmental factors

Frontal traumatic brain injury in rats causes long-lasting impairments in impulse control that are differentially sensitive to pharmacotherapeutics and associated with chronic neuroinflammation.

Traumatic brain injury (TBI) affects millions yearly, and is increasingly associated with chronic neuropsychiatric symptoms. We assessed the long-term effects of different bilateral frontal controlled cortical impact injury severities (mild, moderate, severe) on the five-choice serial reaction time task, a paradigm with relatively independent measurements of attention, motor impulsivity and motivation. Moderately- and severely-injured animals exhibited impairments across all cognitive domains that were still evident 14 weeks post-injury, while mild-injured animals only demonstrated persistent deficits in impulse control. However, recovery of function varied considerably between subjects such that some showed no impairment (“TBI-resilient”), some demonstrated initial deficits that recovered (“TBI-vulnerable”) and some never recovered (“chronically-impaired”). Three clinically-relevant treatments for impulsecontrol or TBI, amphetamine, atomoxetine, and amantadine, were assessed for efficacy in treating injury-induced deficits. Susceptibility to TBI affected the response to pharmacological challenge with amphetamine. Whereas sham and TBI-resilient animals showed characteristic impairments in impulse control at higher doses, amphetamine had the opposite effect in chronically-impaired rats, improving task performance. In contrast, atomoxetine and amantadine reduced premature responding but increased omissions, suggesting psychomotor slowing. Analysis of brain tissue revealed that generalized neuroinflammation was associated with impulsivity even when accounting for the degree of brain damage. This is one of the first studies to characterize psychiatric-like symptoms in experimental TBI. Our data highlight the importance of testing pharmacotherapies in TBI models in order to predict efficacy, and suggest that neuroinflammation may represent a treatment target for impulse control problems following injury

Nigrostriatal inhibition/activation in females

TH:Cre females with hM3 /hM4 in SNc, dosed during acquisition or baseline of cued rG

shinyRGT: An R-Shiny application for extraction and visualization of Rat Gambling Task data

The Rat Gambling Task (RGT) is a well validated rodent model of addiction-like behaviour. It is based on the Iowa Gambling Task (IGT) - a commonly used clinical assay to measure gambling-like behaviour. Rats choose between 4 options to earn as many sugar pellets as possible within 30 min. Each option is associated with dif- ferent reward sizes, but also the probability and duration of the time out punishment. The task is designed such that the optimal strategy for earning sugar pellets is to favour the low risk, low reward options. Consistently selecting the high risk, high reward options results in longer and more frequent time-out penalties. Currently, there is no specialized graphical user interface (GUI) designed to extract, clean, and process RGT data. The installation and use of existing tools are challenging for users lacking coding experience and can be extremely time consuming. To address these issues, we developed a free and open source R-Shiny application called shinyRGT, as a GUI for RGT data extraction, wrangling, and visualization. Clean and usable data can be easily extracted. As well, publication ready plots can be readily generated and annotated from user input. All generated tables can be downloaded as CSV files and generated graphs can be saved to local machines. shinyRGT is deployed at https://andrewcli.shinyapps.io/shinyRGT/for online use. The repository is available at https://github.com/andr3wli/ shinyapps

Increased motor impulsivity in a rat gambling task during chronic ropinirole treatment: potentiation by win-paired audiovisual cues

International audienc

Decreased risk‐taking and loss‐chasing after subthalamic nucleus lesion in rats

International audienceThe subthalamic nucleus (STN) is known to play a role in the control of impulsivity of action and in impulsivity of choice under certain conditions. In order to assess its influence on decision-making under uncertainty, we have tested here the effects of bilateral STN lesions in rats performing a probability discounting task (PDT) and a "loss-chasing" task, both tasks assessing risky decision under uncertainty, but one in a positive context (probability to obtain a larger reward) and the other in a negative context (risk for a larger loss). The PDT measures the choice between a small certain and a large uncertain reward. Conversely, in the "loss-chasing" task, animals choose between accepting a small certain loss versus risking a larger but uncertain penalty. The results show that STN lesions reduce risk-taking in both the PDT and the loss-chasing task, suggesting that STN inactivation could decrease risky decision-making whatever the nature of the outcome in an ambiguous context. Interestingly, opposite results were found in a small number of animals for which the lesions extended to the area dorsal to the STN (in the zona incerta), such that these animals increased choice of the uncertain option in the PDT. These results confirm the specificity of STN involvement in these processes and may provide explanations for some side-effects reported in patients when STN manipulations extend to the Zona Incerta. They also support the choice of the STN as a target for the treatment of impulse control disorders in Parkinson's disease and in obsessive compulsive disorders

Decreased risk‐taking and loss‐chasing after subthalamic nucleus lesion in rats

International audienceThe subthalamic nucleus (STN) is known to play a role in the control of impulsivity of action and in impulsivity of choice under certain conditions. In order to assess its influence on decision-making under uncertainty, we have tested here the effects of bilateral STN lesions in rats performing a probability discounting task (PDT) and a "loss-chasing" task, both tasks assessing risky decision under uncertainty, but one in a positive context (probability to obtain a larger reward) and the other in a negative context (risk for a larger loss). The PDT measures the choice between a small certain and a large uncertain reward. Conversely, in the "loss-chasing" task, animals choose between accepting a small certain loss versus risking a larger but uncertain penalty. The results show that STN lesions reduce risk-taking in both the PDT and the loss-chasing task, suggesting that STN inactivation could decrease risky decision-making whatever the nature of the outcome in an ambiguous context. Interestingly, opposite results were found in a small number of animals for which the lesions extended to the area dorsal to the STN (in the zona incerta), such that these animals increased choice of the uncertain option in the PDT. These results confirm the specificity of STN involvement in these processes and may provide explanations for some side-effects reported in patients when STN manipulations extend to the Zona Incerta. They also support the choice of the STN as a target for the treatment of impulse control disorders in Parkinson's disease and in obsessive compulsive disorders