Effect of tolerance to morphine, ethanol and barbiturate on amphetamine circling in rats with a striatal dopamine lesion.

Abstract

The (+)-amphetamine circling rate of rats with unilateral 6-OHDA lesions in the striatum was recorded. Morphine tablets were implanted subcutaneously for chronic treatment. In the morphine-dependent animal the circling rate to amphetamine given 4 days after morphine was first implanted was depressed but after withdrawal with naloxone a day later the rate increased, returning to normal after 21 days. Barbiturate physical dependence was induced by adding increasing amounts of barbitone to the drinking water of lesioned rats over four weeks after which the amphetamine circling response was depressed and remained so after the barbituate was withdrawn. Ethanol tolerance was induced by adding ethanol to the drinking water of lesioned rats for four weeks. Neither the induction of tolerance over this period nor ethanol withdrawal had any effect on the circling response to amphetamine. The change in the response of striatal dopamine neurons to amphetamine that occurs after chronic morphine treatment, cannot be produced by chronic treatment with either barbitone or ethanol. The neurochemical bases of barbiturate and ethanol tolerance are different from morphine tolerance.