Serotonergic involvement in the inhibitory effects of repeated buspirone treatment on synaptic transmission in the hippocampus.

The effects of acute and long-term treatment with buspirone on synaptic transmission in the hippocampus were compared in alert rats with chronic indwelling electrodes and cannula. Buspirone produced a transient dose-dependent reduction in the amplitude of the excitatory postsynaptic potential (EPSP) when acutely injected either systemically (0.3-3.0 mg/kg i.p.) or directly into the hippocampus (0.1-1.0 microgram i.h.). Whereas acute application of 0.5 mg/kg i.p. produced a 20% reduction which reversed within 2 h, during long-term treatment with this relatively low dose there was a gradual reduction of the baseline EPSP amplitude which reached a maximum (40%) between days 7-14 and which did not reverse completely until 72 h after the last injection. Intrahippocampal injection of either buspirone or 5-hydroxytryptamine did not have any additional effect during the period of baseline reduction. The 5-HT1A receptor antagonist spiroxatrine (1 mg/kg i.p.) produced a transient reversal of the effect of chronic buspirone. It is concluded that the chronic inhibitory effect of buspirone is probably an extension of its acute action on 5-HT1A receptors in the hippocampus.