Individual differencs in dopamine release but not rotational behavior correlate with extracellular amphetamine levels in caudate putament in unlesioned rats |
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Authors: | P. Clausing D. Bloom G. D. Newport R. R. Holson W. Slikker J. F. Bowyer |
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Affiliation: | (1) Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, 72079 Jefferson, AR, USA;(2) Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, 3900 NCTR Road, 72079 Jeffereson, AR, USA |
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Abstract: | It has been postulated that differences in pharmacokinetics do not contribute to the well-known individual variability in response to amphetamine (AMPH), but this is yet to be investigated thoroughly. Therefore, rotational behavior of outbred rats (Sprague-Dawley, 4 months old) was recorded during microdialysis sessions and striatal microdialysate was analyzed concomitantly for AMPH and dopamine concentrations after a single injection of 2.5 mg/kg AMPH SC. Three hours later these rats received three dose of 5mg/kg AMPH SC (spaced 2 h apart) and their brain temperature was recorded every 20 min. The most important findings were: 1) the increase in extracellular dopamine was highly correlated with the corresponding peak AMPH levels in the microdialysate; 2) the peak dopamine level in response to 2.5 mg/kg AMPH was predictive of the hyperthermic response observed during 3×5 mg/kg AMPH and 3) high versus low rotators differed neither in their AMPH nor in their dopamine extracellular striatal concentrations. |
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Keywords: | Amphetamine Pharmacokinetics Microdialysis Dopamine Rotational behavior Hyperthermia Brain temperature Unlesioned rats Individual differences |
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