Potentiated reinstatement of cocaine-seeking behavior following D-amphetamine infusion into the basolateral amygdala

Abstract

Reinstatement of extinguished drug-seeking behavior following chronic drug self-administration has been demonstrated in rats in the presence of conditioned cues. This experimental model of cue-induced relapse can be used to assess the neural circuitry involved in relapse. We have previously shown that blockade of dopamine D1 receptors in the basolateral amygdala (BLA) abolishes conditioned cue-induced reinstatement of cocaine-seeking behavior. The present study tested the hypothesis that D-amphetamine-induced facilitation of monoamine neurotransmission in the BLA would potentiate conditioned cue-induced reinstatement of extinguished drug-seeking behavior. During daily self-administration sessions over 10 consecutive days, rats pressed a lever to receive cocaine infusions (0.2 mg/0.05 ml) paired with a light+tone compound stimulus. Following self-administration, rats underwent daily extinction sessions, during which no stimuli were presented. On the test days, rats received intra-BLA D-amphetamine (10 or 30 micro g/side) or vehicle infusions followed by extinction or conditioned cue-induced reinstatement testing. D-amphetamine infusions did not alter extinction responding relative to vehicle infusions. During reinstatement testing, conditioned cue presentation significantly increased responding over extinction levels, and intra-BLA D-amphetamine produced a dose-dependent increase in lever responding relative to vehicle infusions. These findings suggest that enhanced monoamine tone in the BLA potentiates the motivational effect and/or salience of cocaine-paired cues during reinstatement.