Adaptive changes in 5‐HT1A 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‐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. 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‐HT1A 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‐HT1A receptor‐mediated transmission in the hippocampus. 1994 British Pharmacological Society