Cue-induced conditioned activity does not incubate but is mediated by the basolateral amygdala

Abstract

Re-exposure to drug-associated cues causes significant drug craving in recovering addicts, which may precipitate relapse. In animal models of craving, drug-seeking responses for contingent delivery of drug-associated cues sensitizes or “incubates” across drug withdrawal. To date there is limited evidence supporting an incubation effect for behaviors mediated by non-contingent presentation of drug-associated cues. Here we used a model of cue-induced conditioned activity to determine if the conditioned locomotor response to a non-contingent presentation of a drug-associated cue sensitizes across drug withdrawal. In addition, because cue-induced drug-seeking responses are mediated by the rostral basolateral amygdala (BLA), we investigated whether this structure is critical for the expression of cue-induced conditioned activity. A conditioned association between cocaine (15mg/kg) and a compound discrete cue (flashing bicycle light+a metronome) was established over 12 conditioning sessions in male Sprague–Dawley rats. In experiment 1, cue-induced conditioned activity was assessed on 3 occasions: 3, 14 and 28days following the final drug–cue conditioning session. Cocaine-conditioned rats demonstrated reliable cue-induced conditioned activity across all 3 test sessions, however there was no evidence of an incubation effect. To determine whether repeated testing prevented the observation of an incubation effect, rats in experiment 2 were tested either 3days or 28days following conditioning; again no incubation effect was observed. In experiment 3, either saline or the GABAA receptor agonist muscimol was infused prior to testing. Intra-BLA infusions of muscimol prevented the expression of cue-induced conditioned activity. These data support the role of the rBLA in mediating conditioned responses to drug-associated cues. The failure to observe an incubation effect for cue-induced conditioned activity may point to a fundamental difference in the manner by which contingent and non-contingent presentations of drug-associated cues influence behavior.