ADAPTIVE-CHANGES IN 5-HT1A RECEPTOR-MEDIATED HIPPOCAMPAL INHIBITION IN THE ALERT RAT PRODUCED BY REPEATED 8-OH-DPAT TREATMENT

1 The effect of acute and repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A, receptor ligand, on excitatory amino acid-mediated synaptic transmission was examined in the stratum radiatum CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2 Acute administration of 8-OH-DPAT transiently reduced the amplitude of the field excitatory postsynaptic potential (e.p.s.p.) in a dose-dependent (25-75 mu g kg(-1), i.p.) manner. This effect was blocked by the postsynaptic 5-HT1A receptor antagonist, MDL 73005EF (2 and 4 mg kg(-1), i.p.). 3 8-OH-DPAT (25 mu g kg(-1), i.p.) administered daily for 7 days produced a gradual reduction in the 24 h pre-injection baseline field e.p.s.p. amplitude. The reduction reached its lowest level after 7-8 days and was transiently reversed by acute injection of MDL 73005EF (2 mg kg(-1), i.p.) on day 8. The field e.p.s.p. baseline amplitude recovered fully 5-8 days after cessation of drug treatment. 4 8-OH-DPAT (25 mu g kg(-1), i.p.) administered daily for 7 days produced a marked reduction in acute response to 8-OH-DPAT (25 and 50 mu g kg(-1), i.p.) which did not recover until between day 36 and day 80 of the study. 5 It was concluded that repeated treatment with 8-OH-DPAT produced adaptive changes which resulted ill a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippocampus.