Augmentation of serotonin-induced inhibition of neuronal activity in the hippocampus following repeated treatment with methamphetamine

Electrophysiological studies were performed to determine whether or not hippocampal serotonergic modulation was affected following repeated administration of methamphetamine (MAP). Rats were i.p. administered with MAP (5 mg/kg) or saline once a day for 5 days. Hippocampal slices were prepared at 24 h, 5 and 10 days after the final MAP or saline injection. The population spikes (PS) induced by stimulation of Schaffer collateral/commissural 91 fibers were recorded in the hippocampal CA1 region. Application of serotonin (5-HT) via a bath perfusion system inhibited the PS in a concentration-dependent manner. At 24 h after the final injection, 10-mu M 5-HT-induced inhibition of PS was not affected by MAP treatment. However, 5 days after the final injection, the inhibition by 5-HT (10 mu M) of PS was significantly augmented in the MAP-treated group. Ten days after the final injection, this augmentation was not statistically significant compared with that of control group. 8-OH-DPAT, a 5-HT1A receptor agonist, inhibited PS, but the inhibition was not enhanced or reduced 5 days after the final MAP treatment. However, the enhancement of PS by RS 67333, a 5-HT4 receptor agonist, was attenuated 5 days after the MAP treatment. It was found that 5-HT-induced inhibition of PS in the hippocampal CA1 region was potentiated 5 days after cessation of MAP, and this effect was suggested to be due to reduction of excitatory 5-HT4 receptor functions.