Caudate-putamen dopamine and stereotypy response profiles after intravenous and subcutaneous amphetamine

We compared the behavioral and caudate-putamen extracellular dopamine respo nses following intravenous (3.6 mg/kg) and subcutaneous (8 mg/kg) amphetami ne administration using 2-min microdialysate sampling intervals, and doses of the drug selected to achieve comparable maximal brain concentrations. Fo llowing intravenous amphetamine, dopamine peaked within the first 2 min, th en declined with a first-order decay rate of 0.018 +/- 0.007 min(-1). Follo wing subcutaneous amphetamine, dopamine achieved maximum concentrations at 9 min and remained near peak levels for about 30 min before declining with a first-order decay rate of 0.019 +/- 0.008 min(-1). Maximal brain amphetam ine levels and peak dopamine concentrations were equivalent following eithe r route of drug administration. In contrast to the short latency to maximal extracellular dopamine, the onset of oral stereotypies was delayed until a bout 30 min following both routes of drug administration. Furthermore, in c ontrast to the behavioral response to amphetamine, apomorphine administrati on resulted in the rapid appearance of oral stereotypies within 5-10 min af ter drug administration. These results suggest that although caudate-putame n dopamine receptor activation may be a critical factor in the expression o f focused oral stereotypies, other effects of amphetamine may interfere wit h the ability of animals to exhibit these behaviors. Synapse 31:125-133, 19 99. (C) 1999 Wiley-Liss, Inc.