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 micrograms 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 micrograms 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 micrograms kg-1, i.p.) administered daily for 7 days produced a marked reduction in acute response to 8-OH-DPAT (25 and 50 micrograms 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 in a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippocampus.
Department of Pharmacology & Therapeutics, University of Dublin, Ireland.
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Manahan-Vaughan
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Anwyl
M J
MJ
Rowan
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000222:Adaptation, Physiological; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D011985:Receptors, Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin