TY - JOUR T1 - Extracellular Dopamine and Amphetamine After Systemic Amphetamine Administration: Comparison to the Behavioral Response JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 591 LP - 596 VL - 282 IS - 2 AU - Ronald Kuczenski AU - William P. Melega AU - Arthur K. Cho AU - David S. Segal Y1 - 1997/08/01 UR - http://jpet.aspetjournals.org/content/282/2/591.abstract N2 - To further delineate amphetamine-dopamine pharmacokinetic-pharmacodynamic relationships, we examined extracellular levels of dopamine and amphetamine 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 achieving maximum concentrations within 30 min of drug administration. Tissue levels of amphetamine exhibited a similar, although slightly earlier time to maximum levels. The concentrations of amphetamine and dopamine in the extracellular fluid and amphetamine in tissue rapidly declined with similar rates of elimination. In contrast to the temporal profiles for both dopamine and amphetamine, stereotyped behaviors achieved maximum intensity at about 60 min. In addition, although transmitter and drug declined almost 10-fold from maximum values over the 4-hr interval after amphetamine administration, stereotyped behaviors persisted for at least 3 hr before abating. The results of these studies confirm our previous observation that the temporal profiles for stereotyped behaviors and extracellular dopamine are dissociated, and also extend this dissociation to extracellular amphetamine. In addition, although 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 responsiveness to amphetamine. The American Society for Pharmacology and Experimental Therapeutics ER -