Modeling impulsivity

We use well-established models of impulsive action and impulsive choice to answer a variety of different research questions. Given that the neural and neurochemical systems controlling these behaviours are broadly known, we can use these paradigms to answer more complex questions that typically involve a combination of both pharmacology and molecular biology.  Here are some of the ways in which are using models of impulsivity to understand impulse control in health and disease.

High impulsivity is a feature of several psychiatric conditions, including bipolar disorder. For example, manic episodes can lead to risky and inappropriate behaviours, such as drug and alcohol binges, or excessive gambling. Lithium is the “gold standard” pharmacotherapy for bipolar disorder yet its mechanism of action remains unknown. Molecular studies show that lithium has widespread cellular and intracellular effects—the challenge is determining which of these actions contribute to lithium’s ability to improve symptoms. As lithium may decrease the severity of mania and reduce suicidality in bipolar disorder by reducing impulsivity, we are investigating the effects of chronic lithium treatment in an animal model of motor impulsivity, the five-choice serial reaction time task (5CSRT).  Lithium is administered orally via a custom diet containing lithium chloride to bring serum levels within the therapeutic range seen in human patients. Molecular assays are exploring the neurochemical basis of lithium’s effects on behaviour, with a focus on immune markers implicated in the neuroprogressive nature of bipolar disorder.

Deficits in impulse control are also prominent in conditions of excessive and uncontrollable eating, such as binge eating disorder and obesity. Evidence in the literature suggests that highly palatable foods, like those high in fats and sugar, might be ‘addictive’, which is a topic of some controversy. Given the relationship between impulsivity and addiction, we are exploring whether long-term consumption of high-fat or high-sugar foods can influence impulsivity in the 5CSRT. Complementary experiments, conducted in collaboration with Prof. Timothy Kieffer (Department of Cellular and Physiological Sciences), are using leptin-deficient rats (‘Kilorats’) to assess whether pathologically obese animals show cognitive deficits in the 5CSRT. Molecular assays will measure dopaminergic markers in subcortical brain regions involved in impulsivity and addiction, as well as plasma levels of metabolic markers related to glucose and fat metabolism.

One of the most successful and widely used models of impulsive decision-making which has been adapted for use with rodents is the delay-discounting paradigm. Both humans and animals find delay to reward delivery aversive i.e. the value of a reward can be discounted by the delay to its delivery. Although a large reward is normally valued more highly than a smaller reward, if the delay to the delivery of large reward is relatively long compared to the small reward, the subjective value of the small reward increases relative to the large reward and may surpass it. At this point, the individual may choose impulsively i.e. select a small immediate over a larger but delayed reward. Highly impulsive populations, such as those with ADHD, bipolar disorder, or substance abuse disorder, show steeper discounting curves i.e. shift their preference from large to small rewards even when the delay to the large reward is relatively short.

We, and others, have shown that this form of impulsive decision-making can be influenced by dopaminergic manipulations, and that this behaviour is controlled by key nodes within the affective cortico-striatal loop. Furthermore, some evidence suggests that there may be competing circuits in the brain, one promoting impulsive choice (including the orbitofrontal cortex and subthalamic nucleus), the other self-control (including the nucleus accumbens and basolateral amygdala). Asymmetrical disconnection experiments can determine whether such a hypothesis is true. We are also interested in understanding how using a cue to signal the duration of the delay decreases levels of impulsive decision-making, potentially due to recruitment of dopaminergic signalling in the orbitofrontal cortex.