Augmentation of Serotonin-Induced Inhibition of Neuronal Activity in the Hippocampus Following Repeated Treatment with Methamphetamine

doi:10.1196/annals.1316.030

Present address for correspondence: K. Ishihara, Ph.D., Laboratory of Neuropharmacology, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure 737-0112, Japan. Voice: +81-823-73-8926; fax: +81-823-73-8981. ishihara{at}ps.hirokoku-u.ac.jp
Ann. N.Y. Acad. Sci. 1025: 242-247 (2004).

Electrophysiological studies were performed to determine whetheror not hippocampal serotonergic modulation was affected followingrepeated administration of methamphetamine (MAP). Rats werei.p. administered with MAP (5 mg/kg) or saline once a day for5 days. Hippocampal slices were prepared at 24 h, 5 and 10 daysafter the final MAP or saline injection. The population spikes(PS) induced by stimulation of Schaffer collateral/commissuralfibers were recorded in the hippocampal CA1 region. Applicationof serotonin (5-HT) via a bath perfusion system inhibited thePS in a concentration-dependent manner. At 24 h after the finalinjection, 10-µM 5-HT-induced inhibition of PS was notaffected by MAP treatment. However, 5 days after the final injection,the inhibition by 5-HT (10 µM) of PS was significantlyaugmented in the MAP-treated group. Ten days after the finalinjection, this augmentation was not statistically significantcompared with that of control group. 8-OH-DPAT, a 5-HT_1A receptoragonist, inhibited PS, but the inhibition was not enhanced orreduced 5 days after the final MAP treatment. However, the enhancementof PS by RS 67333, a 5-HT₄ receptor agonist, was attenuated5 days after the MAP treatment. It was found that 5-HT-inducedinhibition of PS in the hippocampal CA1 region was potentiated5 days after cessation of MAP, and this effect was suggestedto be due to reduction of excitatory 5-HT₄ receptor functions.