Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement

Psychopharmacology (Berl). 1996 Oct;127(3):213-24.


In these experiments we sought to establish the intravenous (i.v.) self-administration of cocaine under a second-order schedule of reinforcement in order: (i) to obtain reliable, drug-free levels of responding with cocaine as a reinforcer, and (ii) to enable investigation of the neural mechanisms by which arbitrary cues gain motivational salience and, as conditioned reinforcers, control over drug-seeking behaviour. Initially, each infusion of cocaine was made contingent upon a response on one of two identical levers and was paired with a 20-s light conditioned stimulus (CS). Responses on the second lever were recorded, but had no programmed consequence. When rats acquired stable rates of self-administration, a second-order schedule of the type FRx(FRy:S) was introduced, with values of "x" being increased progressively to 10 and then "y" from 2 through 8. Priming (i.e. non-contingent) infusions of cocaine were never given. Once the first infusion was obtained under the second-order schedule, further infusions were made contingent on each response (to a maximum of ten infusions/day). Each stage was repeated daily until the first infusion of each session was achieved within a 5-min criterion. Rats with bilateral, excitotoxic lesions of the basolateral amygdala readily acquired the i.v. self-administration of cocaine under a continuous reinforcement schedule, initially administering more infusions and maintaining a slightly elevated level of self-administration than controls. Despite increased numbers of CS/drug pairings, basolateral amygdala-lesioned rats were severely impaired in the acquisition of the second-order schedule of i.v. cocaine reinforcement. Lesioned rats showed a cocaine dose-response function that was shifted upwards relative to control subjects. There was no significant difference between drug-naive amygdala-lesioned and control animals in the locomotor response to intraperitoneal injections of cocaine. These experiments 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 mechanisms underlying cocaine-taking and cocaine seeking behaviour, and demonstrate the potential importance of the basolateral amygdala in the processes by which previously neutral stimuli gain control over drug-seeking behaviour.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects*
  • Amygdala / pathology
  • Animals
  • Behavior, Animal / drug effects*
  • Brain Diseases / chemically induced
  • Brain Diseases / pathology
  • Cocaine / administration & dosage*
  • Conditioning, Operant
  • Male
  • Narcotics / administration & dosage*
  • Quinolinic Acid
  • Rats
  • Self Administration


  • Narcotics
  • Quinolinic Acid
  • Cocaine