Collections > Electronic Theses and Dissertations > Neuronal encoding of habit-like alcohol self-administration in the rat dorsal striatum

Alcoholism is characterized by persistent drinking that may involve a shift from goal-directed to habitual drinking as behavior becomes engrained and resistant to treatment. Recent evidence suggested these behaviors have distinct anatomical substrates, with the dorsomedial striatum (DMS) implicated in goal-directed behavior, while the dorsolateral striatum (DLS) was required for habit formation. It was unknown, however, whether these regions are differentially activated during habitual alcohol reinforcement and what role specific neurotransmitter systems in the DLS might play in habitual alcohol drinking. The studies described here investigated how DMS and DLS neurons encode cues, actions, and reward deliveries during operant self-administration via extracellular recordings from chronically implanted electrodes. Our central hypothesis was 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. First, we characterized dorsal striatal electrophysiology during goal-directed versus habitual models of alcohol self-administration, and found distinct DMS and DLS activation in both models. DLS outcome-related activation was greater for unpredictable reward delivery in the more habitual model. Next, systemic dopamine receptor antagonism reduced alcohol seeking and baseline firing rates without modulating neuronal activation to session-start cues. In the final series of experiments, neuronal firing patterns were compared in rats self-administering sweetened alcohol versus sweet solutions alone. Alcohol was found to promote DMS activation, while the most habitual rats in the same model showed less DLS outcome activation. Unilateral dopamine receptor antagonism proximal to recording electrodes reduced overall baseline firing rates in the DLS, while bilateral DLS antagonism reduced habit-like reward seeking and phasic DMS neuronal activation during action selection. In sum, these studies suggest that DMS and DLS cooperatively promote reward seeking, and habitual behavior requires DLS dopaminergic activation but not a reduction in DMS activation. These innovative and mechanistic studies significantly advance our understanding of the neural substrates of habitual alcohol seeking and drinking behavior, and elucidate the dependence of behavioral inflexibility on dopamine. Thus, these studies uncover physiological correlates of behavioral resistance to change, providing new avenues for future treatment of alcohol use disorder.