Basolateral amygdala lesions retard extinction of cocaine-seeking behavior and cocaine-conditioned place preference.

摘要

Incentive motivation for cocaine elicited by cocaine-associated stimuli is thought to be involved in craving and relapse. To examine the role of the basolateral amygdala complex (BLC) in this phenomenon, the effects of post-training BLC lesions on extinction of cocaine-seeking behavior and cocaine-conditioned place preference (CPP) and the effects of pre-training BLC lesions on acquisition of cocaine-CPP were assessed. In Exp. 1, rats were first trained to self-administer cocaine, and then received bilateral excitotoxic (0.12 M N-methyl-D-aspartic acid; 0.3 mul/side) or sham BLC lesions. Subsequently, they were tested for extinction of cocaine-seeking behavior (i.e., nonreinforced responses in the presence of cocaine-paired stimuli). Rats were then trained and tested for acquisition of cocaine-CPP (i.e., increased time spent in a previously cocaine-paired, relative to a saline paired, environment). Locomotion, compartment entries, and acquisition of fear conditioning (i.e., freezing behavior in a previously shock-paired environment) were measured as behavioral controls. In Exp. 2, rats were first trained and tested for cocaine-CPP, and then received excitotoxic or sham BLC lesions. They were then tested repeatedly for extinction of cocaine-CPP. Post-training BLC lesions retarded extinction of cocaine-seeking behavior and cocaine-CPP, whereas pre-training lesions impaired acquisition of cocaine-CPP and freezing behavior. Only a transient lesion-induced increase in locomotion and no effect on compartment entries were observed. We suggest pre-training BLC lesions disrupted acquisition of cocaine-CPP by impairing assignment of incentive value to cocaine-paired stimuli, whereas post-training BLC lesions retarded extinction of cocaine-conditioned behaviors by impairing assessment of the current incentive value of cocaine-paired stimuli.