Generalized habitual tendencies in alcohol dependent rats

Habitual responses and ultimately compulsive behavior are thought to be at the core of addiction including alcohol use disorder (AUD). Little is known whether the habitization concerns exclusively the response towards alcohol or generalizes to other daily activities. Here, we address this question in a well-established animal model of AUD - the postdependent rat model - by testing habitual responses towards a sweet palatable reward in two striatal learning paradigms: spatial navigation and reward conditioning. For the spatial navigation task, alcohol-dependent and control rats were tested on a sequential decision-making test after short and prolonged T-Maze training; for the reward conditioning task, rats were trained under a random interval schedule for a short and prolonged period and tested in a satiety devaluation test at each time point. Another cohort of alcohol-naive rats was trained and tested on both paradigms under DREADD (designer receptors exclusively activated by designer drugs)-mediated inactivation of the dorsomedial striatum (DMS) which controls goal-directed behavior. Our results show that alcohol-dependent rats displayed increased habitual behavior to obtain saccharin reward on both paradigms, with overall more habitual choices after prolonged training on the spatial navigation task, and increased habitual responses already after short training on the reward conditioning task. Finally, DREADD-mediated inactivation of the DMS increased habitual behavior in non-dependent rats on both paradigms. Our results provide evidence that a history of alcohol dependence produces a bias towards habitual responding that generalizes to a natural reward in rats. Similarly, a habitual bias was induced in non-dependent rats after inactivation of the DMS, thus confirming the critical role of this region in maintaining goal-directed behavior and suggesting its diminished control in AUD.