Grant: Operating Grant

Neurons using the neurotransmitter serotonin (5-HT) project widely through the brain, and 5-HT alters neuronal function via multiple receptors. Given the ubiquitous and complex nature of 5-HT signalling it is not surprising that manipulations of 5-HT function alter a wide range of different behaviours, and that 5-HT has been implicated in many psychiatric disorders including anxiety, depression, schizophrenia, impulse control disorders, eating disorders and addiction. My research has found that activating 5-HT2C receptors reduces addiction-like behaviour and impulsiveness. Blocking the 5-HT2A receptor also reduces some of these behaviours. The present proposal explores the potential clinical utility of 5-HT2C receptor agonists and 5-HT2A receptor antagonists for treating "motivational" disorders such as addiction, impulsivity and abnormal feeding. We are especially interested in 1) how these drugs alter nicotine self-administration, relapse to nicotine seeking and impulsiveness, 2) the sites in the brain that mediate the effects of these drugs, and the circuits that mediate these different behaviours, and 3) how 5-HT2A receptor blockade and 5-HT2C receptor activation alter dopamine function.