Title: Adaptive changes in 5‐HT<sub>1A</sub> receptor‐mediated hippocampal inhibition in the alert rat produced by repeated 8‐OH‐DPAT treatment
Abstract: The effect of acute and repeated treatment with 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin (8‐OH‐DPAT), a 5‐HT 1A 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. 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 μg kg −1 , i.p.) manner. This effect was blocked by the postsynaptic 5‐HT 1A receptor antagonist, MDL 73005EF (2 and 4 mg kg −1 , i.p.). 8‐OH‐DPAT (25 μg 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. 8‐OH‐DPAT (25 μg kg −1 , i.p.) administered daily for 7 days produced a marked reduction in acute response to 8‐OH‐DPAT (25 and 50 μg kg −1 , i.p.) which did not recover until between day 36 and day 80 of the study. It was concluded that repeated treatment with 8‐OH‐DPAT produced adaptive changes which resulted in a reduction in the dynamic range of 5‐HT 1A receptor‐mediated transmission in the hippocampus.