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. 2021 Jul 20;46(12):2121–2131. doi: 10.1038/s41386-021-01096-1

Fig. 4. Effect of Intra-VTA, Intra-CeA and Intra-NAc Administration of LY2817412 on Cue‐Induced Reinstatement of Alcohol Seeking in Male and Female msP rats.

Fig. 4

A Schematic representation of the experimental timeline. B–D Conditioning phase: black circles (male) and white circles (female) represent the responses during the last 3 days of alcohol self‐administration; black squares (male) and white squares (female) represent the responses during the last 3 days of water self-administration during the discrimination phases. Analysis of this phase showed a significant time × drugs interaction in all brain regions for the active lever presses. No differences were denoted for the inactive lever. Extinction: mean number of lever presses during the last 3 days of extinction (EXT). B Male (n = 7) and female (n = 7) rats were implanted with bilateral cannulas aimed at the VTA. Compared to EXT, rats exposed to alcohol-predictive of discriminative stimuli (S+/CS+) and treated with LY2817412 vehicle (0.0) reinstated active lever pressing. Intra-VTA administration of the drug attenuated the reinstatement elicited by the alcohol-predictive discriminative stimuli. C Male (n = 7) and female (n = 8) rats were implanted with bilateral cannulas aimed at the CeA. Compared to EXT, rats exposed to alcohol-predictive of discriminative stimuli (S+/CS+) and treated with LY2817412 vehicle (0.0) reinstated active lever pressing. Intra-CeA administration of the NOP antagonist did not prevent the effect of S+/CS+. D Male (n = 8) and female (n = 8) msP rats were implanted with bilateral cannulas aimed at the NAc. Compared to EXT, rats exposed to the alcohol-predictive stimuli (S+/CS+) elicited a significant reinstatement of responding. Intra-NAc administration of the NOP antagonist did not prevent the effect of S+/CS+. Presentation of water paired cues (S−/CS−) never affected operant responding that in all groups remained at extinction level. Values represent the mean (±SEM). ###p < 0.001, difference between EXT and rats exposed to alcohol paired cues (S+/CS+) treated with LY2817412 vehicle (0.0); °°p < 0.001, difference in the reinstatement between male and female msP rats; ***p < 0.001, difference between rats presented with S+/CS+ and LY2817412 vehicle (0.0) and rats treated different doses of the antagonist.