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BACKGROUND Individuals addicted to cocaine spend much of their time foraging for the drug Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence especially when presented response-contingently acting as conditioned reinforcers that bridge delays to drug use The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala BLA and the nucleus accumbens core NAcC However the precise neuronal circuits underlying the acquisition of cue-controlled cocaine-seeking behavior have not been elucidated METHODS Here we used a projection-specific Cre-dependent DREADD designer receptor exclusively activated by designer drugs -mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine-seeking behavior RESULTS In Sprague Dawley rats with Cre-mediated expression of the inhibitory DREADD hM4D Gi in the NAcC-projecting BLA neurons treatment with clozapine N-oxide but not vehicle selectively prevented the impact of cocaine-associated conditioned reinforcers on cocaine seeking under a second-order schedule of reinforcement This effect was attributable to the chemogenetic inhibition of the NAcC-projecting BLA neurons as it was reversible and it was absent in clozapine N-oxide-treated rats expressing an empty control virus In contrast chemogenetic inhibition of the anterior insula which receives collateral projections from NAcC-projecting BLA neurons was without effect CONCLUSIONS These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues requires activity in the direct projections from the BLA to the NAcC Leverhulme Trust

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The Basolateral Amygdala to Nucleus Accumbens Core Circuit Mediates the Conditioned Reinforcing Effects of Cocaine-Paire...

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with Second-order schedule of reinforcement as keyword