Cortical Evoked Potential Changes During Classical Conditioning of Morphine Dependence in Rats.

A classical conditioning experiment was designed to determine if a conditioned neural response would develop and persist in cortical evoked potentials elicited by a foreleg stimulus (CS+) that was paired with morphine administration during the development of dependence and subsequent withdrawal. A stimulus to the other foreleg (CS−) was presented explicitly unpaired with morphine delivery. After dependence was established, the rats were taken from the experimental chamber and withdrawn from morphine for 6 days in their home cages. Finally, during the testing phase, the animals were returned to the experimental chamber and the foreleg stimuli were presented. The CS+ was paired with either morphine or saline injections. Changes due to both morphine effects only and conditioning were observed. The conditioned response, however, was present only in the cortical evoked potentials recorded from those animals receiving contralateral foreleg stimulation as the CS+. The conditioned neural response persisted after withdrawal and was present in both the drug-free and morphine-intoxicated animals. These results provide support for the relapse theory that a nonextinguished conditioned response is retained after withdrawal. However, further experiments are necessary to determine if these conditioned responses can elicit drug-seeking behavior.