Momentary increases in impulsive behavior, including increases in disinhibition or lapses in self-control or attention, may increase drug use and especially relapse to drug use. This project will investigate variables that increase or decrease impulsive behavior, with the goal of eventually relating these to susceptibility to relapse to cigarette smoking. Impulsive behavior will be measured using standardized tasks assessing decision-making (i.e., delay discounting), behavioral inhibition (i.e., Stop Task performance) and attention. In the first series of studies we will investigate variables that acutely increase impulsive behavior, including acute stress, sleep deprivation, administration of alcohol, and, in cigarette smokers, nicotine deprivation. In the second series of studies we will investigate factors that decrease impulsive behavior, including acute administration of the stimulant drugs amphetamine and bupropion. In the third series of studies we will determine whether stimulant drugs prevent the acute increases in impulsive behavior induced by environmental events. Finally, we propose to develop a laboratory model of smoking relapse to study the role of impulsivity in relapse. In this model, we plan to test whether, and to what extent, variables that affect impulsive behavior affect susceptibility to relapse. Throughout all of these studies, we will continue our investigation of the subtypes of impulsive behavior and other cognitive processes. We will investigate the relationships between impairments in decision-making, inhibition and attention, and begin to investigate their role in relapse. Understanding the underlying factor structure of impulsive behavior is important from both basic science and clinical perspectives. In combination with parallel studies being conducted with non-humans, these projects will improve our knowledge of the neurobiology of impulsive behavior. Clinically, the projects may lead to novel strategies for preventing and treating substance abuse. ? ?
| Gorka, Stephanie M; Fitzgerald, Daniel A; de Wit, Harriet et al. (2014) Cannabinoid modulation of amygdala subregion functional connectivity to social signals of threat. Int J Neuropsychopharmacol 18: |
| Rabinak, Christine A; Sripada, Chandra Sekhar; Angstadt, Mike et al. (2012) Cannabinoid modulation of subgenual anterior cingulate cortex activation during experience of negative affect. J Neural Transm (Vienna) 119:701-7 |
| Palmer, Abraham A; de Wit, Harriet (2012) Translational genetic approaches to substance use disorders: bridging the gap between mice and humans. Hum Genet 131:931-9 |
| Hamidovic, Ajna; Childs, Emma; Conrad, Megan et al. (2010) Stress-induced changes in mood and cortisol release predict mood effects of amphetamine. Drug Alcohol Depend 109:175-80 |
| Vaughn, Linda K; Denning, Gerene; Stuhr, Kara L et al. (2010) Endocannabinoid signalling: has it got rhythm? Br J Pharmacol 160:530-43 |
| McCloskey, Michael; Palmer, Abraham A; de Wit, Harriet (2010) Are attention lapses related to d-amphetamine liking? Psychopharmacology (Berl) 208:201-9 |
| Lejuez, C W; Magidson, Jessica F; Mitchell, Suzanne H et al. (2010) Behavioral and biological indicators of impulsivity in the development of alcohol use, problems, and disorders. Alcohol Clin Exp Res 34:1334-45 |
| Hamidovic, Ajna; Dlugos, Andrea; Palmer, Abraham A et al. (2010) Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine. Psychiatr Genet 20:85-92 |
| Potenza, Marc N; de Wit, Harriet (2010) Control yourself: alcohol and impulsivity. Alcohol Clin Exp Res 34:1303-5 |
| Hamidovic, Ajna; de Wit, Harriet (2009) Sleep deprivation increases cigarette smoking. Pharmacol Biochem Behav 93:263-9 |
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