EXTRACELLULAR DOPAMINE AND AMPHETAMINE AFTER SYSTEMIC AMPHETAMINE ADMINISTRATION - COMPARISON TO THE BEHAVIORAL-RESPONSE

To further delineate amphetamine-dopamine pharmacokinetic-pharmacodyna mic relationships, we examined extracellular levels of dopamine and am phetamine in caudate-putamen after the s.c. administration of 8 mg/kg amphetamine. In a parallel group of animals, we also assessed caudate- putamen tissue levels of the drug. Extracellular concentrations of the transmitter and the drug exhibited similar temporal profiles, each ac hieving maximum concentrations within 30 min of drug administration. T issue levels of amphetamine exhibited a similar, although slightly ear lier time to maximum levels. The concentrations of amphetamine and dop amine in the extracellular fluid and amphetamine in tissue rapidly dec lined with similar rates of elimination. In contrast to the temporal p rofiles for both dopamine and amphetamine, stereotyped behaviors achie ved maximum intensity at about 60 min. In addition, although transmitt er and drug declined almost 10-fold from maximum values over the 4-hr interval after amphetamine administration, stereotyped behaviors persi sted for at least 3 hr before abating. The results of these studies co nfirm our previous observation that the temporal profiles for stereoty ped behaviors and extracellular dopamine are dissociated, and also ext end this dissociation to extracellular amphetamine. In addition, altho ugh there was a close correspondence between dopamine and amphetamine within each experimental animal, individual animals exhibited a broad range of maximal dopamine responses, suggesting a differential respons iveness to amphetamine.