Basolateral amygdala lesions impair both cue- and cocaine-induced reinstatement in animals trained on a discriminative stimulus task.

Drug-associated environmental cues can maintain drug use and contribute to relapse even after long periods of abstinence. We investigated the ability of sensory stimuli that signaled periods of reward availability to sustain cocaine self-administration and trigger the reinstatement of reward-seeking behavior. We demonstrate that lesions of the basolateral amygdala (BLA), a structure strongly implicated in attributing salience to environmental stimuli, significantly reduced the power of predictive cues to elicit reward-seeking behavior. In daily training sessions, a 20 s discriminative stimulus (DS) was presented to rats on a variable interval schedule. If five lever presses were recorded during the DS-on period, then cocaine (0.5 mg/kg) and a conditioned stimulus (CS) were simultaneously delivered. After training, half the animals received excitotoxic lesions of the BLA with quinolinic acid; the other half received saline. Compared with sham-lesioned animals, rats with BLA lesions earned fewer cocaine injections and were less accurate in responding to the DS in the first few days following the lesion. However, they maintained the same cocaine intake as sham-lesioned animals when the DS requirement was lifted. Finally, after seven extinction sessions, reinstatement was measured in response to: 1) i.v. cocaine infusion, 2) DS, 3) CS, 4) a familiar, but non-rewarded cue (S-) or 5) no stimulus. In sham-lesioned animals, cocaine and the DS, but not the CS or the S-, triggered reinstatement. BLA lesions abolished DS-induced reinstatement and significantly attenuated cocaine-induced reinstatement. These results demonstrate 1) that when tested under the same conditions, a discriminative cue which signals reward availability is a more robust trigger of reward-seeking than a Pavlovian CS which signals reward delivery and 2) that the BLA contributes to reinstatement in response to these discriminative cues.