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-pr opylamino)tetralin (8-OH-DPAT), a 5-HT1A, receptor ligand, on excitato ry amino acid-mediated synaptic transmission was examined in the strat um radiatum CA1 region of the dorsal hippocampus of alert, gently rest rained, 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 wa s 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.) administ ered daily for 7 days produced a gradual reduction in the 24 h pre-inj ection baseline field e.p.s.p. amplitude. The reduction reached its lo west level after 7-8 days and was transiently reversed by acute inject ion of MDL 73005EF (2 mg kg(-1), i.p.) on day 8. The field e.p.s.p. ba seline amplitude recovered fully 5-8 days after cessation of drug trea tment. 4 8-OH-DPAT (25 mu g kg(-1), i.p.) administered daily for 7 day s produced a marked reduction in acute response to 8-OH-DPAT (25 and 5 0 mu g kg(-1), i.p.) which did not recover until between day 36 and da y 80 of the study. 5 It was concluded that repeated treatment with 8-O H-DPAT produced adaptive changes which resulted ill a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippoca mpus.