Repository logo

The Basolateral Amygdala to Nucleus Accumbens Core Circuit Mediates the Conditioned Reinforcing Effects of Cocaine-Paired Cues on Cocaine Seeking.

Accepted version

No Thumbnail Available



Change log


Puaud, Mickaël 
Higuera-Matas, Alejandro 
Brunault, Paul 
Everitt, Barry J 


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.



Basolateral amygdala, Chemogenetics, Cocaine, Conditioned reinforcement, Nucleus accumbens core, Second-order schedule of reinforcement, Animals, Basolateral Nuclear Complex, Cocaine, Cues, Drug-Seeking Behavior, Nucleus Accumbens, Rats, Rats, Sprague-Dawley, Self Administration

Journal Title

Biol Psychiatry

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Leverhulme Trust (RPG-2016-117)
Medical Research Council (MR/N02530X/1)
Leverhulme Trust