Clinical Neuroscience

Section Head

Contact

Dr. Usoa Busto
Clinical Neuroscience
Centre for Addiction and Mental Health
33 Russell Street
Toronto, Ontario M5T 1R8
u soa_busto@camh.net

Research Objective

The section investigates the neurobiological basis of substance use and gambling disorders in human subjects. Our objective is to better understand the risk factors that contribute to gambling and substance use disorders including genetic factors, psychiatric comorbidities, intrinsic pharmacological properties of drugs, and drug kinetics. Although nicotine has been used as the model for current studies, scientists plan to expand the model to include alcohol and mood disorders.

Summary of Activities

Recently our section has been concentrating on the study of the acute versus chronic drug effect of drugs and craving, and on psychiatric comorbidity using imaging techniques.

In the comorbidity area, researchers submitted a Positron Emission Tomography (PET) study of dopamine release in subjects meeting criteria for both nicotine dependence and depression to the Archives of General Psychiatry.

Researchers in this section are also involved in the pharmacoextinction of smoking behaviours and there are on-going projects in this area in collaboration with CAMH’s Addictions Medicine Clinic. Researchers are also collaborating on:

Neuroimaging studies with CAMH’s Translational Addiction Research Laboratory, the PET Centre, and Toronto Western Hospital’s Department of Radiology;
The electrophysiological, cognitive-behavioural, and motivational effects of the antiseizure medication, topiramate on stress-induced responses to gambling in male and female pathological gamblers with high and low negative emotionality;
Developing an animal model of gambling-induced dopamine dysfunction; and
Several aspects of pathological gambling (Letters of Intent have been approved for three collaborative grant applications).

Summary of recent achievements: Demonstrated that: (1) patients with depression and comorbid nicotine dependence have a dysfunctional dopaminergic system both at baseline and after the administration of a dopamine agonist (d-amphetamine); (2) amphetamine “cross-primes” gambling motivation in problem gamblers; and (3) partial dopamine blockade by haloperidol increases gambling reward/motivation in problem gamblers. Evaluated that: Modafinil as pharmacotherapy for problem gambling (patent application has been filed).

The Clinical Neuroscience Lab at CAMH is also the only laboratory in Canada conducting preclinical drug administration research into the psychopharmacology and cognitive-behavioural mechanisms of gambling in pathological gamblers.

Publications

Busto UE, Redden L, Mayberg H, Kapur S, Houle S, Zawertailo LA. Dopaminergic System Function in Depressed Smokers: A Positron Tomography Study. Submitted to Archives of General Psychiatry, January 2007.

Zack M, Poulos CX, Aramakis VB, Khamba BK, MacLeod CM. Effects of drink-stress sequence and gender on alcohol stress response dampening in high and low anxiety sensitive drinkers. Alcohol Clin Exp Res. 2007;31(3):411-22.

Zack M, Poulos CX. A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers. Neuropsychopharmacology. 2007 Jan 3. Advance online publication.

Zack M, Poulos CX, Woodford TM. Diazepam dose-dependently increases or decreases implicit priming of alcohol associations in problem drinkers. Alcohol. 2006;41(6):604-10.

Zack M, Poulos CX, Fragopoulos F, Woodford TM, MacLeod CM. Negative affect words prime beer consumption in young drinkers. Addict Behav. 2006;31(1):169-73.

Glass J, Lanctot KL, Herrman N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risk and benefits. British Medical Journal. 2005;331:1169-1176.

Tremblay, LK, Naranjo CA, Graham SJ, Herrmann N, Mayberg HS, Hevenor S, Busto UE. Functional neuroanatomical substrates of altered reward processing in Major Depressive Disorder revealed by a dopaminergic probe. Archives of General Psychiatry. 2005;62:1228-1236