Augmentation of the behavioral and electrophysiologic response to cocaine by chronic administration in the rat

Abstract

Previous experiments have demonstrated an augmentation of the behavioral effects of cocaine with chronic administration. Cocaine has a pronounced electrophysiologic effect in the basal forebrain, and it was hypothesized that the repetition of this effect during chronic administration might result in an augmentation of the electrophysiologic and behavioral responses to the drug, similar to those seen to electrical stimulation in the kindling phenomenon of G. V. Goddard (1967. Nature (London)214: 1020–1021). Male Sprague-Dawley rats were implanted with electrodes in the amygdala. After recovery, they were administered saline or one of two doses of cocaine for 13 days. The chronic administration of the high dose of cocaine resulted in augmentation of its behavioral and electrophysiologic effects. Subsequently the animals were given daily electrical stimulation of the amygdala to determine if the chronic cocaine administration had produced an effect in the amygdala which would facilitate kindling. No significant facilitation was found, although this finding was considered inconclusive. A subsequent test injection of cocaine indicated that the augmentation of the electrophysiologic response to cocaine persisted for an average of 20 days or more. Persistence of the augmented behavioral effect was also found. Possible mechanisms underlying this augmentation were discussed.