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Evidence for postsynaptic mediation of the hypothermic effect of 5‐HT 1A receptor activation
Author(s) -
O'Connell M.T.,
Sarna G.S.,
Curzon G.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14382.x
Subject(s) - postsynaptic potential , neuroscience , receptor , mediation , chemistry , biology , biochemistry , political science , law
1 The 5‐HT 1A ligand BMY 7378 (8‐[2[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]8‐azaspirol [4,5]‐decane‐7,9‐dione dihydrochloride, 0.032–2 mg kg −1 , s.c.) caused hyperphagia, a response to the activation of presynaptic 5‐HT 1A receptors. 2 BMY 7378 (8 mg kg −1 , s.c.) and the 5‐HT 1A agonist (8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT), 0.10 and 0.25 mg kg −1 s.c.) also caused hypothermia. This was inhibited by (−)‐pindolol (1 mg kg −1 , i.p.) and not prevented by pretreatments with p‐chlorophenylalanine which grossly depleted 5‐hydroxytryptamine (5‐HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5‐HT 1A receptors. Infusion of BMY 7378 (8–64 μg) into the dorsal raphe was without convincing hypothermic effect. 3 BMY 7378 (8 mg kg −1 , s.c.) inhibited another effect of activation of postsynaptic 5‐HT 1A receptors, i.e., the induction of components of the 5‐HT syndrome by 8‐OH‐DPAT (0.5, 1.0 mg kg −1 , s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites. 4 Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED 50 (hypothermia) > 2 mg kg −1 , ED 50 (hyperphagia) = 0.010 mg kg −1 . This contrasts with the similar ED 50 values for both the hypothermic (ED 50 = 0.08–0.10 mg kg −1 ) and hyperphagic (ED 50 = 0.06–0.10 mg kg −1 ) effects of 8‐OH‐DPAT. 5 The evidence obtained for mediation of the hypothermic response to 5‐HT 1A agonists by postsynaptic sites is relevant to the interpretation of the effects on it of antidepressant treatments and depressive illness.