Both animal and human models of alcoholism etiology have focused on biobehavioral response to alcohol as a potential marker of alcoholism risk vulnerability and disease progression. Alcoholism has been conceptualized in neurobiological models as a transition from positive reinforcement (i.e., """"""""drinking to feel good"""""""") to negative reinforcement (i.e., """"""""drinking not to feel bad or to feel normal""""""""), representing a cycl of progressive neurobiological dysregulation. Alcohol administration studies in the human laboratory allow for the translation of preclinical theory to clinical populations through examination of the subjective response to alcohol (comprising stimulation, sedation and tension relieving dimensions) at different levels of drinking status (i.e. heavy drinking or alcohol dependent groups). To date, no studies have used alcohol administration paradigms to translate neurobiological models of alcoholism etiology to clinical populations. The objective of this application is to examine well-established neurobiological theories of alcoholism etiology in the human laboratory. To do so this study combines traditional alcohol challenge and progressive ratio self-administration methodologies to elucidate the relationship between subjective response to alcohol and one's willingness to work for alcohol. In order to model the transition from positively to negatively reinforced alcohol use two groups (n total = 82) will be recruited, a group of non- dependent heavy drinkers and a group of alcohol dependent individuals. An exploratory aim will examine candidate genes subserving the positive and negative reinforcing effects of alcohol. The proposed study extends the alcoholism literature through testing neurobiologically informed hypotheses about the moderating role of drinking status on subjective response to alcohol in the lab and the relationship between subjective response and self-administration of additional alcohol ad lib.
Alcoholism is a debilitating and costly psychiatric disorder whose neurobiological underpinnings remain poorly understood. Neurobiological models have garnered considerable evidence in preclinical research but have yet to be translated to clinical samples with alcoholism. The proposed research will test neurobiologically-driven hypotheses about subjective response to alcohol and alcohol self-administration in the human laboratory, thus translating animal models of alcoholism neurobiology to clinical samples.
