Methamphetamine administration reduces hippocampal vesicular monoamine transporter-2 uptake.

Rau KS, Birdsall E, Volz TJ, Riordan JA, Baucum AJ, Adair BP, Bitter R, Gibb JW, Hanson GR, Fleckenstein AE
J Pharmacol Exp Ther. 2006 318 (2): 676-82

PMID: 16687477 · DOI:10.1124/jpet.105.099200

Repeated high-dose injections of methamphetamine (METH) rapidly decrease dopamine uptake by the vesicular monoamine transporter-2 (VMAT-2) associated with dopaminergic nerve terminals, as assessed in nonmembrane-associated vesicles purified from striata of treated rats. The purpose of this study was to determine whether METH similarly affects vesicular uptake in the hippocampus; a region innervated by both serotonergic and noradrenergic neurons and profoundly affected by METH treatment. Results revealed that repeated high-dose METH administrations rapidly (within 1 h) reduced hippocampal vesicular dopamine uptake, as assessed in vesicles purified from treated rats. This reduction was likely associated with serotonergic nerve terminals because METH did not further reduce vesicular monoamine uptake in para-chloroamphetamine-lesioned animals. Pretreatment with the serotonin transporter inhibitor fluoxetine blocked both this acute effect on VMAT-2 and the decrease in serotonin content observed 7 days after METH treatment. In contrast, there was no conclusive evidence that METH affected vesicular dopamine uptake in noradrenergic neurons or caused persistent noradrenergic deficits. These findings suggest a link between METH-induced alterations in serotonergic hippocampal vesicular uptake and the persistent hippocampal serotonergic deficits induced by the stimulant.

MeSH Terms (17)

Animals Benzylamines Data Interpretation, Statistical Dopamine Dopamine Uptake Inhibitors Fluoxetine Male Methamphetamine Neurons p-Chloroamphetamine Rats Rats, Sprague-Dawley Serotonin Serotonin Agents Serotonin Uptake Inhibitors Synaptic Vesicles Vesicular Monoamine Transport Proteins

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