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Queen's University
 

MotiCog Lab

Research: Impulsivity in Addiction

Learning to Inhibit a Response

Effective interaction with the world around us depends on the ability to modify behaviour in response to environmental cues. These cues provide information on appropriate cues, not only which responses are correct but when they should be initiated. Standing at the intersection in any major city makes this point obvious: failing to wait for the green light can have disastrous consequences. My research group has focused on understanding these impulsive actions which we describe as ‘right move, wrong time’. To facilitate this work, Scott Hayton designed the Response Inhibition (RI) task in which rats withhold lever pressing for sucrose until a signal is presented. Responses prior to the signal are a measure of impulsive action. Advantages of the RI task include the fact that it is acquired rapidly, it provides measures of individual differences across rats, and both increases and decreases in performance can be observed following experimental manipulations. The RI task allowed Scott Hayton and Matt Lovett-Barron to test the novel hypothesis that impulse control requires new learning. We confirmed this idea in a collaboration with Eric Dumont (Dept. of Molecular and Biomedical Sciences), by showing that impulsive action is encoded as enhanced glutamate transmission in projections from the prelimbic (PL) region of the medial prefrontal cortex (mPFC) to the ventral striatum (VS). A follow up study revealed increased membrane excitability in the same neurons, providing further support for a specific mechanism underlying the acquisition of impulse control. An unexpected and intriguing outcome of this study was that plasticity in the adjacent infralimbic (IL) cortex encodes learning about cues predicting reward availability. Thus, there may be a functional dissociation across IL and PL cortices in the control of impulsive action.


Publications:


Hayton, S.J., Olmstead, M.C., & Dumont, E.C. (2011). Shift in the intrinsic excitability of medial prefrontal cortex neurons following training in impulse control and cued responding tasks. Public Library of Science (PLoS) One, 6, e23885.

Hayton, S.J., Lovett-Barron, M., Dumont, E.C. & Olmstead, M.C. (2010). Target-specific encoding of response inhibition: Increased contribution of AMPA to NMDA receptors at excitatory synapses in the prefrontal cortex. Journal of Neuroscience, 30, 11493-11500.

Olmstead, M.C. (2006). Animal models of drug addiction: Where do we go from here? Quarterly Journal of Experimental Psychology, 59, 625-53.

Pharmacology of Impulsive Action

Impulsive action, defined as the inability to inhibit a response (in lay terms ‘acting without thinking’) is linked to a number of neurotransmitter systems.  These include dopamine, serotonin, glutamate, and cannabinoids among others.  In collaboration with Prof. Brigitte Kieffer’s team at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg France, we provided the first evidence for an opioid contribution to impulsive action. In this study, deletion of mu opioid receptors in mice decreased impulsive action whereas deletion of delta opioid receptors had the opposite effect. We extended these findings by showing that opioid drugs alter impulsive action in rats, but the data were not consistent with the genetic knockout studies. This led us reconsider the role of other neurotransmitters in impulsive action, leading to the idea that inhibition of a motor response is controlled by different cognitive processes, depending on the task demands. Scott Hayton, Amanda Maracle and Megan Mahoney helped to verify this conjecture by showing that amphetamine and morphine have distinct effects on impulsive action when rats can and cannot predict the delay to reward availability. To understand the role of timing in this dissociation, we examined the probability of responding across sessions, revealing unique patterns of time-dependent errors under different task conditions. We are now examining whether differences in the cognitive processes that inhibit responding help to explain individual differences in trait impulsivity.

Publications:

Mahoney, M.K., Silveira, M.M., & Olmstead, M.C. (2013). Increased impulsive action in rats: Effects of morphine in a short and long fixed-delay response inhibition task. Psychopharmacology, 230, 569-577.
 
Hayton, S.J., Maracle, A.C., & Olmstead, M.C. (2012).  Opposite effects of amphetamine on impulsive action with fixed and variable delays to respond.  Neuropsychopharmacology, 37, 651-659. 

Befort, K., Mahoney, M.K., Chow, C., Hayton, S.J., Kieffer, B.L. & Olmstead, M.C. (2011). Effects of delta opioid receptor activation on a response inhibition task in rats. Psychopharmacology, 214, 967-976.

Olmstead, M.C., Ouagazzal, A. & Kieffer, B.L. (2009). Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task. Public Library of Science (PLoS) One, 4, e4410.

Paine, T.A. & Olmstead, M.C. (2004). Cocaine disrupts both behavioural inhibition and conditional discrimination in rats. Psychopharmacology, 175, 443-450.

 

Binge Drinking

Our work with animal models of addiction and impulsivity is used to test hypotheses regarding the relationship between the two.  Iris Balodis directed a complementary line of research, translating this preclinical work to humans. We focused on university students, a population that exhibits high rates of drug use and risky behaviours (related to impulsivity).  To date, we have shown that self-reported levels of impulsivity correlate with both recreational drug use and hazardous drinking; the latter is also associated with enhanced conditioning to reward-paired cues. Recently we reported that hormonal responses to stress are blunted by an alcohol placebo, and that initial hormonal reactions to the lab predict later responses to alcohol.  On the other hand, contrary to lay assumptions, alcohol intoxication does not increase risky choices in a gambling task or alter reward-related learning.  In contrast, stress-responses (both subjective and biochemical) are markedly reduced by alcohol.  Moreover, initial hormonal reactions to a laboratory setting predict subsequent responses to alcohol, which may be a biomarker for stress-related responses. The work furthers our understanding of how intoxication leads to impulsive behaviours, such as drinking and driving or unprotected sex.  This research has many practical implications because it furthers our understanding of why intoxication leads to dysfunctional behaviours; this information may then be applied to social interventions designed to reduce the incidence of problems associated with alcohol intoxication. The ultimate goal of this work is to identify factors which predict individuals who will develop maladaptive drinking and drug use during their undergraduate years.

Publications:

Mahoney, M.K., & Olmstead, M.C. (2013). Neurobiology of an endophenotype: Modelling the progression of alcohol addiction in rodents. Current Opinions in Neurobiology, 23, 607-614.
 
Magrys, S.A., & Olmstead, M.C. (2014). Alcohol intoxication alters cognitive skills mediated by frontal and temporal brain regions. Brain and Cognition, 85, 271-276.

Magrys, S.A., Wynne-Edwards, K.E., Olmstead, M.C., & Balodis, I.S. (2013). Biochemical responses to alcohol intoxication in healthy males: relationship with impulsivity, drinking behaviour and subjective effects.  Psychophysiology, 50, 204-209.

Mahoney, M.K., & Olmstead, M.C. (2013). Neurobiology of an endophenotype: Modelling the progression of alcohol addiction in rodents. Current Opinions in Neurobiology, 23, 607-614.

Magrys, S.A., & Olmstead, M.C. (2014). Alcohol intoxication alters cognitive skills mediated by frontal and temporal brain regions. Brain and Cognition, 85, 271-276.

Magrys, S.A., Wynne-Edwards, K.E., Olmstead, M.C., & Balodis, I.S. (2013).  Biochemical responses to alcohol intoxication in healthy males: relationship with impulsivity, drinking behaviour and subjective effects.  Psychophysiology, 50, 204-209.

Balodis, I.S., Wynne-Edwards, K.E. & Olmstead, M.C. (2011). The stress-response-dampening effect of placebo. Hormones & Behavior, 59, 465-472.

Balodis, I.M., Wynne-Edwards, K.E. & Olmstead, M.C. (2010). The other side of the curve: examining the relationship between pre-stressor physiological responses and stress reactivity. Psychoneuroendocrinology, 35, 1363-1373.

Balodis, I.M. Lockwood, K.L. Magrys, S.A. & Olmstead, M.C. (2010). Preference conditioning in healthy individuals correlates with hazardous drinking. Alcoholism: Clinical and Experimental Research, 34, 1006-1012.

Balodis, I.M., Potenza, M.N. & Olmstead, M.C. (2010). Recreational drug use and impulsivity in a population of Canadian undergraduate drinkers. Frontiers in Psychiatry, 1, 1-7.

Balodis, I.M., Potenza, M.N. & Olmstead, M.C. (2009). Binge drinking in undergraduates: Binge drinking in undergraduates: Relationships with gender, drinking behaviors, impulsivity and the perceived effects of alcohol. Behavioural Pharmacology, 20, 518-526.

Balodis, I.M., Johnsrude, I.S. & Olmstead, M.C. (2007). Intact preference conditioning in acute intoxication despite deficient declarative knowledge and working memory. Alcoholism: Clinical and Experimental Research, 31, 1800-1810.

Balodis, I.M., MacDonald, T.K. & Olmstead, M.C. (2006). Instructional cues modify performance in the Iowa Gambling Task. Brain and Cognition, 60, 109-17.

Kingston, Ontario, Canada. K7L 3N6. 613.533.2000