Abbreviations used: DA, dopamine; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine or serotonin; METH, methamphetamine.
Attenuation and Recovery of Evoked Overflow of Striatal Serotonin in Rats Treated with Neurotoxic Doses of Methamphetamine
Article first published online: 19 MAR 2003
Journal of Neurochemistry
Volume 74, Issue 3, pages 1079–1085, March 2000
How to Cite
Cass, W. A. (2000), Attenuation and Recovery of Evoked Overflow of Striatal Serotonin in Rats Treated with Neurotoxic Doses of Methamphetamine. Journal of Neurochemistry, 74: 1079–1085. doi: 10.1046/j.1471-4159.2000.0741079.x
- Issue published online: 19 MAR 2003
- Article first published online: 19 MAR 2003
Abstract: Repeated administration of methamphetamine to animals can lead to long-lasting decreases in striatal monoamine content. In the present study, the effects of neurotoxic doses of methamphetamine on basal and evoked overflow of striatal serotonin and of its primary metabolite 5-hydroxyindoleacetic acid were examined in awake rats using in vivo microdialysis. Male Fischer-344 rats were administered methamphetamine (5 mg/kg, s.c.) or saline four times in 1 day at 2-h intervals. Microdialysis studies were carried out 1 week, 1 month, and 6 months later. At 1 week posttreatment there were significant decreases in potassium- and amphetamine-evoked overflow of serotonin in the striatum of the methamphetamine-treated animals. Basal extracellular levels of 5-hydroxyindoleacetic acid but not of serotonin were also decreased. Evoked overflow of serotonin recovered by 1 month, and extracellular levels of 5-hydroxyindoleacetic acid had recovered by 6 months. Tissue levels of serotonin and 5-hydroxyindoleacetic acid were decreased at 1 week posttreatment but back to control levels by 1 month after treatment. These results indicate that presynaptic serotonergic functioning is attenuated in the striatum of rats treated 1 week earlier with neurotoxic doses of methamphetamine. However, in the model used, the changes are transient, and recovery can occur within 1-6 months posttreatment.