Biopsychology

Section Head

Research Objective

The neurochemical bases of behaviours relevant to addictions and psychiatric disorders are investigated using preclinical models to identify the mechanisms of action of drugs used to treat these disorders.

Summary of Activities

The Section studies the biological foundations of normal and abnormal behaviours relevant to psychiatry. The research focuses on the role that brain neurotransmitter systems, particularly the serotonin and dopamine systems, and the interactions between these systems play in controlling behaviour.

Serotonin receptors and the effects of drugs of abuse

Dopamine is the neurotransmitter most closely linked to the behavioural effects and neurochemical effects of drugs of abuse. However, manipulating serotonin (5-HT) function, particularly at the 5-HT_2C receptor subtypes, alters the behavioural effects of drugs of abuse. Activating the 5-HT_2C receptor reduces the stimulant and reinforcing effects of cocaine, and inhibits reinstatement of cocaine-seeking behaviour. Blocking the 5-HT_2C receptor increases the stimulant and reinforcing effects of cocaine, and enhances cocaine-induced reinstatement of drug-seeking behaviour. Some of the effects of other drugs of abuse are also increased following 5-HT_2C receptor blockade. These data indicate that the 5-HT_2C receptor might be an important target for treating addiction.

Amphetamine sensitization and schizophrenia

In humans, some stimulant users exhibit signs of psychosis. Following repeated, intermittent exposure to amphetamine, some of the effects of this drug become sensitized. The amphetamine-induced sensitized state (AISS) is being used to model aspects of schizophrenia. A recent series of experiments found that the AISS results in cognitive deficits are similar to those observed in schizophrenia. The most pronounced deficits are in sustained visual attention and attentional set-shifting. This latter deficit is particularly intriguing since cognitive flexibility is required to successfully perform the Wisconsin Card Sorting Test, a task poorly performed by schizophrenia patients. The deficits in the AISS model are reversed by injecting a dopamine D₁ receptor agonist into the prefrontal cortex. Future plans involve using this model to test potential treatments, including D₁ receptor agonists, for cognitive disturbances in schizophrenia.