Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior

Abstract

Following a Pavlovian pairing procedure, alcohol-paired cues come to elicit behavioral responses that lead to alcohol consumption. Here we used an optogenetic approach to activate basolateral amygdala (BLA) axonal terminals targeting the shell of nucleus accumbens (AcbSh) and investigated a possible influence over cue-conditioned alcohol seeking and alcohol drinking, based on the demonstrated roles of these areas in behavioral responding to Pavlovian cues and in feeding behavior. Rats were trained to anticipate alcohol or sucrose following the onset of a discrete conditioned stimulus (CS). Channelrhodopsin-mediated activation of the BLA-to-AcbSh pathway concurrent with each CS disrupted cued alcohol seeking. Activation of the same pathway caused rapid cessation of alcohol drinking from a sipper tube. Neither effect was accompanied by an overall change in locomotion. Finally, the suppressive effect of photoactivation on cued-triggered seeking was also evidenced in animals trained with sucrose. Together these findings suggest that photoactivation of BLA terminals in the AcbSh can override the conditioned motivational properties of reward-predictive cues as well as unconditioned consummatory responses necessary for alcohol drinking. The findings provide evidence for a limbic-striatal influence over motivated behavior for orally consumed rewards, including alcohol.