Pavlovian cue-evoked alcohol seeking is disrupted by ventral pallidal inhibition

Abstract

Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50% of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.

Keywords: Pavlovian; alcohol; cues; ventral pallidum.

Figure 1.. Viral approach and targeting.

A) AAVs coding for the expression of ArchT-YFP or YFP alone were bilaterally infused into the ventral pallidum (VP) and optic fibers were cemented in place over the injection sites. B) Representative YFP expression localized to the VP. C) Summary of optic fiber tip locations within the VP.

Figure 2.. Pavlovian alcohol seeking training data.

A) Schematic of the Pavlovian conditioned alcohol seeking task, where a CS+ cue predicts alcohol delivery into a reward port, and a CS− cue has no associated outcomes. B, D, F, H) Across training acquisition, rats in the ArchT and YFP-only viral groups learned to discriminate the alcohol predictive CS+ from the CS−. C) Port entry probability, E) number of port entries, F) port entry latency (s), H) and port time (s), differed by cue type in each viral group by the end of training. Data presented as mean +/− SEM. Dots represent individual animals.

Figure 3.. Pre-cue port entries during training.

Across training acquisition A) pre-cue port entries decreased for both viral groups, and B) were equal by the end of training. Data presented as mean +/− SEM. Dots represent individual animals.

Figure 4.. Ventral pallidum inhibition acutely disrupts Pavlovian conditioned alcohol seeking.

A) Schematic of the optogenetic manipulation. Green laser was delivered on 50% of CS+ and CS− trials. B) Port entry probability during the CS+ was reduced in the ArchT group on laser stimulation trials. C) Port entry probability was not affected by laser delivery in the YFP group. D) The number of port entries during the CS+ was reduced on laser trials for the ArchT group. E) The number of port entries during the CS+ was reduced on laser trials for the YFP group. F) The latency (s) to make port entries during the CS+ was increased on laser trials for the ArchT group. G) There was no effect of laser delivery on port entry latency for the YFP group. H) The time rats spent in the alcohol port (s) during the CS+ was also reduced during laser trials in the ArchT group. I) There was no impact of laser on port entry time for the YFP group.