Alcoholism is characterized by persistent drinking that may involve a shift from goal-directed to habitual drinking as the behavior becomes engrained and resistant to treatment. Recent evidence suggests these behaviors have distinct anatomical substrates, with the dorsomedial striatum (DMS) implicated in goal-directed behavior, while the dorsolateral striatum (DLS) is required for habit formation. It remains unknown, however, whether these regions are differentially activated during alcohol reinforcement and what role specific neurotransmitter systems in the DLS might play in habitual alcohol drinking. The studies proposed here will investigate how DMS and DLS neurons encode cues, actions, and reward deliveries during operant self- administration of alcoholic versus non-alcoholic rewards via extracellular recordings from chronically implanted electrodes. These neuronal firing patterns will be compared in a model of alcohol self-administration commonly used to generate habitual alcohol seeking: a variable interval schedule. Next, electrophysiology will be combined with local pharmacology to investigate the role of dopamine in the DLS on behavior as well as firing patterns of dorsal striatal neurons. Our central hypothesis is that the expression of habitual behavior depends on parallel circuits acting in competition, with sensorimotor processing in the DLS exhibiting greater activation and behavioral control during habit-like alcohol self-administration. These innovative and mechanistic studies will significantly advance our understanding of the neural substrates of habitual alcohol seeking and drinking behavior, and elucidate whether this behavioral inflexibility is dependent on dopamine. Understanding the neurobiology underlying this critical aspect of alcoholism will be necessary for the future of prevention and treatment of this chronic disease. In addition, the training proposed here will provide a strong technical and educational foundation and promote a productive career in addiction neurobiology.
Alcohol abuse is a significant public health concern in the United States, but the neural substrates underlying the formation and reversal of alcohol drinking habits are not well understood. The studies proposed here will examine the impact of alcohol on neuronal activity during habitual reward-seeking behavior. This work has the potential to elucidate signaling mechanisms necessary for habitual alcohol drinking, which may be novel targets for the prevention and treatment of alcoholism.
|Fanelli, Rebecca R; Robinson, Donita L (2015) Dopamine D1 receptor blockade impairs alcohol seeking without reducing dorsal striatal activation to cues of alcohol availability. Brain Behav 5:e00305|