Abstract
Amphetamine (AMPH) appears to release dopamine (DA) from a newly synthesized cytoplasmic (nonvesicular) pool, independent of neurogenic activity. However, norepinephrine (NE) is presumed to be synthesized exclusively in vesicles and recent studies have shown AMPH-induced increases in extracellular NE to be partially dependent on impulse flow. In order to elucidate the contribution of vesicular catecholamines (CA) to the AMPH response, in vivo microdialysis in freely moving rats was used to examine the effects of reserpine (RES), which disrupts vesicular stores of CA, on the caudate DA and hippocampus NE responses to AMPH. These results were compared to the effects of cocaine (COC), which depend on vesicular stores of CA and impulse flow-mediated exocytosis. As anticipated, the NE responses to both AMPH (0.5, 1.25, and 5.0 mg/kg) and COC (20 mg/kg) were prevented by RES pretreatment (2.5 mg/kg, 24h). Also, whereas RES did not alter the DA response to the intermediate dose of AMPH, it decreased the DA responses to the low and high doses of AMPH by about 65% and 50%, respectively. Furthermore, although the DA response to COC was significantly decreased by RES, it was not completely prevented. In summary, the dopaminergic and noradrenergic responses to AMPH and COC exhibited both predicted and unanticipated dependence on vesicular stores of CA. Dissociations between biochemistry and behavior will be discussed.
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Florin, S., Kuczenski, R. & Segal, D. Effects of Reserpine on Extracellular Caudate Dopamine and Hippocampus Norepinephrine Responses to Amphetamine and Cocaine: Mechanistic and Behavioral Considerations. Neuropsychopharmacol 11, 268 (1994). https://doi.org/10.1038/sj.npp.1380146
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DOI: https://doi.org/10.1038/sj.npp.1380146