The use of d -amphetamine pellet implantation as a model for d -amphetamine tolerance in the mouse

Abstract

The use of d -amphetamine pellet implantation as a method for producing rapid central drug tolerance was investigated. Mice were implanted with d -amphetamine pellets containing 2 mg of drug and were challenged 24 h later, a time when no detectable drug was present, with various doses of d -amphetamine i.p. Implantation was found to potentiate the stereotyped activity and produced tolerance to the exploratory activity induced by d -amphetamine. Daily pellet implantation for 3 days was not found to produce tolerance to the stereotyped activities. Animals administered a single pellet showed no difference in the brain disposition or metabolism of a subsequent dose of 3 H- d -amphetamine. Twenty-four hour pellet implantation markedly increased the rate of conversion of 3 H-tyrosine to 3 H-dopamine (330%) and 3 H-norepinephrine (61%) in the subcortex. However, this effect was reversed by the administration of 10 mg/kg of d -amphetamine.