Neural circuits regulating punished alcohol-seeking

Sandra Helinski

Andrew Holmes, NIAAA

This presentation will show data from behavioral, genetic and in vivo single-unit recordings that implicate neuronal circuits in the prefrontal cortex and amygdala in regulating alcohol self-administration following shock-induced punishment. Addictions including alcohol use disorders (AUDs) are characterized by the loss of control over the substance seeking and consumption, but the neural circuits and signaling mechanisms responsible for the transition from controlled use to uncontrolled abuse remain incompletely understood. Prior studies have developed measures of ‘compulsive-like drug-seeking’ in rodents that measure persistent responding for ethanol (EtOH) despite footshock or adulteration with an unpleasant taste. We have found that chronic intermittent EtOH (CIE) and leads to attenuated suppression of EtOH-seeking after footshock-punishment in mice. In addition, we have performed chronic single-unit recordings of neurons in the medial prefrontal cortex (mPFC) and amygdala to show that neuronal correlates of punished-suppression of responding for EtOH. This analysis was complimented by fluorescence-based in situ hybridization of punishment-related neuronal activity in the mPFC and amygdala. To establish a causal role for the mPFC in this behavior, we have photosilenced projection neurons in this region during punished EtOH-seeking. Together, our data provide may novel insight into the neural facts underlying the development of resistance to punished EtOH-seeking that characterizes AUDs.