Grant: Project Grant

Alcohol use disorders have detrimental effects on health and society. The neurotransmitter serotonin has been linked to aspects of alcohol use, and is a therapeutic target for several disorders. The main goal of this work is to use animal models to understand the role of serotonin in modulating multiple aspects of alcohol use. We have three main aims. Firstly, using a pharmacological approach we will explore the potential for drugs interacting with serotonin to modulate different aspects of alcohol use, including reinforcement, relapse, dependence and impulsivity. Two drugs that interact with serotonin in different ways are pimavanserin and lorcaserin. They are used to treat Parkinson's disease and obesity, respectively. However, based on their pharmacological actions we predict that they may be useful for treating addiction. We will produce a comprehensive behavioural analysis of the effects of pimavanserin and lorcaserin on multiple aspects of alcohol use and addiction, including measures of alcohol reinforcement (self-administration), binge-drinking, reinstatement of alcohol seeking and alcohol-induced impulsivity. To look at possible sex differences and the impact of past alcohol use, these studies will be done in non-dependent as well as alcohol-dependent male and female animals. Secondly, we will examine underlying mechanisms mediating effects of pimavanserin and lorcaserin on alcohol use. This will be done by measuring changes in brain activity following exposure to alcohol with and without pimavanserin and lorcaserin. We will also assess how lorcaserin and pimavanserin alter alcohol-induced changes in dopamine release, since this neurotransmitter is the one most closely linked to reward-related behaviours. Finally we will determine where in the brain these drugs act to produce their effects. The significance of this work is that it may lead to the testing of clinically used drugs, pimavanserin and lorcaserin, for treating alcohol abuse and addiction.