Differential development of the enhanced metabolic response during amphetamine sensitization

Behavioral sensitization elicited by repeated administration of amphetamine does not fully develop until a period after discontinuation of amphetamine, but then persists undiminished for a long time. This experiment investigated the regional metabolic changes in rats pretreated with amphetamine and challenged after different abstinence periods (2, 7 and 28 days), using the 2-[14C]deoxyglucose method. The results demonstrated that chronic amphetamine administration enhanced rates of local cerebral glucose utilization in specific cerebral regions. The magnitude and distribution of effects varied with the abstinence period. A challenge dose of d-amphetamine 2 days after pretreatment was found to have no more, or only mildly elevated, local cerebral glucose utilization compared with that following a single acute dose. In rats challenged at the 7th and 28th day, a supersensitive metabolic response was found in dopaminergic and non-dopaminergic areas. This finding suggested regional differences in the development of sensitization and underscored the importance of an abstinence period in the study of sensitization and amphetamine psychosis.