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 accompanied 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.

An endocannabinoid-regulated basolateral amygdala–nucleus accumbens circuit modulates sociability

“…Although disruptions in amygdala and NAc function have been demonstrated in ASDs (17)(18)(19), how amygdala-NAc circuit activity relates to sociability deficits in ASD is not well understood. Existing literature on the amygdala, specifically the basolateral amygdala (BLA), indicates that the BLA-NAc circuit regulates learned behavioral choice, including reward seeking, risk-based decision-making, fear, and depression-like behavior, all of which may contribute to changes in social approach and social behaviors (20)(21)(22)(23)(24)(25)(26)(27). Because the BLA-NAc circuit underlies decision-making in response to rewarding cues and subsequent behavioral responses (21,23), we hypothesize that activity in the BLA-NAc circuit may regulate multiple aspects of sociability under physiological conditions and perhaps under conditions of impaired social function.…”

Recruitment and disruption of ventral pallidal cue encoding during alcohol seeking

“…To assess the degree to which VP neurons encode alcohol cues trained on different types of associations, we trained rats in a discriminative stimulus (DS) task or in Pavlovian conditioning, both with 15% ethanol as the reward. Prior to training in each task, rats were pre‐exposed to ethanol in the homecage as described previously (Millan et al., ; Remedios et al., ; Simms et al., ) to acclimatize them to the taste and pharmacological effects of ethanol and allow stabilization of drinking behavior. In the DS task, entry into the reward port during the DS (an auditory cue lasting up to 10 s) resulted in delivery of 15% ethanol and termination of the DS cue, whereas port entries during a control auditory cue (the non‐rewarded stimulus [NS]) or during the inter‐trial interval had no programmed consequences.…”

“…Rats trained with alcohol reward (Alcohol DS or Alcohol CS+ groups) or trained with sucrose reward after alcohol exposure (Suc(alc) DS or Suc(alc) CS+ groups) were pre‐exposed to ethanol in the homecage prior to training as described previously (Millan, Kim, & Janak, ; Remedios, Woods, Tardif, Janak, & Chaudhri, ; Simms et al., ). This was conducted to either: (a) acclimatize them to the taste and pharmacological effects of ethanol and allow stabilization of drinking behavior prior to conditioning with alcohol at the reward (Alcohol DS or Alcohol CS+ groups), or (b) to assess the impact of ethanol exposure itself, in rats that were subsequently conditioned with sucrose reward (Suc(alc) DS or Suc(alc) CS+ groups).…”

Intermittent Ethanol Access Increases Sensitivity to Social Defeat Stress

“…The BLA is implicated in affective disorders and addiction due to its role in stress responses, motivation, and cognition (Sharp, 2017). A projection from the BLA to the NAC shell was recently determined to control voluntary alcohol consumption (Millan et al, 2017), supporting the role of this region in both affect and voluntary intake. As chronic alcohol gavage is not a voluntary form of consumption, this may explain why no differences in activation were observed in the BLA after this exposure.…”