Evoked potential changes during classical conditioning of morphine in the awake, freely behaving rat

Abstract

The phenomena of repeated addict relapse has been attributed to the development of some sort of conditioning or learning process which proceeds concomitant with the development of drug dependence by the addict. It is further thought that these drug-induced conditional responses remain resistant to extinction after addict withdrawal and may be a prime causal factor in the resumption of drug use. To test this hypothesis, rats were surgically prepared with chronic electrodes to record electrocorticograms (ECoG) and an intravenous jugular catheter and subjected to a classical conditioning paradigm of auditory clicks (the conditional stimulus) and a small intravenous infusion of morphine sulfate (the unconditional stimulus). Morphine shifted the ECoG spectral pattern from a predominance of desynchronization to low-frequency (< 6 Hz), high-voltage (200 to 400 μV) slow waves. Three of the four cortical auditory evoked potential (EP) peaks increased in magnitude during morphine administration. Comparisons of EPs from habituation sessions with conditioning sessions indicated that their amplitudes changed during the course of conditioning trials. No changes (conditional or unconditional) were observed in a parallel series of saline-vehicle control subjects. Our findings of central nervous system signs of conditioning indicate that morphine is a powerful agents which may form conditional responses in the human addict and suggest that a permanent cure for addict relapse may require extinction of such conditional responses.