EXCITOTOXIC LESIONS OF THE BASOLATERAL AMYGDALA IMPAIR THE ACQUISITION OF COCAINE-SEEKING BEHAVIOR UNDER A 2ND-ORDER SCHEDULE OF REINFORCEMENT

In these experiments we sought to establish the intravenous (IV) self- administration of cocaine under a second-order schedule of reinforceme nt in order: (i) to obtain reliable, drug-free levels of responding wi th cocaine as a reinforcer, and (ii) to enable investigation of the ne ural mechanisms by which arbitrary cues gain motivational salience and , as conditioned reinforcers, control over drug-seeking behaviour. Ini tially, each infusion of cocaine was made contingent upon a response o n one of two identical levers and was paired with a 20-s light conditi oned stimulus (CS). Responses on the second lever were recorded, but h ad no programmed consequence. When rats acquired stable rates of self- administration, a second-order schedule of the type FRx(FRy:S) was int roduced, with values of ''x'' being increased progressively to 10 and then ''y'' from 2 through 8. Priming (i.e. non-contingent) infusions o f cocaine were never given. Once the first infusion was obtained under the second-order schedule, fur ther infusions were made contingent on each response (to a maximum of ten infusions/day). Each stage was rep eated daily until the first infusion of each session was achieved with in a 5-min criterion. Rats with bilateral, excitotoxic lesions of the basolateral amygdala readily acquired the IV self-administration of co caine under a continuous reinforcement schedule, initially administeri ng more infusions and maintaining a slightly elevated level of self-ad ministration than controls. Despite increased numbers of CS/drug pairi ngs, basolateral amygdala-lesioned rats were severely impaired in the acquisition of the second-order schedule of IV cocaine reinforcement. Lesioned rats showed a cocaine dose-response function that was shifted upwards relative to control subjects. There was no significant differ ence between drug-naive amygdala-lesioned and control animals in the l ocomotor response to intraperitoneal injections of cocaine. These expe riments indicate the feasibility and utility of second-order schedules in studying the neurobehavioural basis of cocaine-seeking behaviour. They suggest a dissociation in the neural mechanisims underlying cocai ne-taking and cocaine seeking behaviour, and demonstrate the potential importance of the basolateral amygdala in the processes by which prev iously neutral stimuli gain control over drug-seeking behaviour.