5-HT1A RECEPTOR-MEDIATED INHIBITION IN THE HIPPOCAMPUS OF THE ALERT RAT - EFFECTS OF REPEATED GEPIRONE TREATMENT

The effects of acute and repeated treatment with the 5-HT1A receptor l igand gepirone on hippocampal excitatory synaptic transmission were in vestigated. Recordings of the electrically evoked field population exc itatory postsynaptic potentials (e.p.s.p.s) were made in the stratum r adiatum of the CA1 region of the dorsal hippocampus of alert male Wist ar rats. Acute injection of gepirone reduced the e.p.s.p. amplitude in a transient dose-dependent (0.5-10 mg/kg, i.p.) manner. This effect w as blocked by the 5-HT1A receptor antagonist MDL 73005 EF (8-[2-(2,3-d ihydro-1,4-benzodioxin-2-yl methylaminoethys]-8-azaspiro[4,5]decane-7, 9-dione methyl sulphonate, 2 mg/kg, i.p.). Gepirone (1 mg/kg per day, i.p.) administered for 7 days produced a gradual reduction in the dail y pre-injection baseline e.p.s.p. amplitude coupled with a concomitant reduction of the acute response to the drug. The chronic baseline red uction was transiently reversed by the 5-HT1A receptor antagonist spir oxatrine and complete recovery to pretreatment levels was observed 48 h after the last gepirone dose. The data indicate that with repeated a dministration, a prolongation and enhancement of the 5-HT1A receptor-m ediated reduction in the e.p.s.p. by gepirone occurs. This delayed eff ect may contribute to the slow onset of therapeutic action of gepirone .