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Actions of 5‐hydroxytryptamine and 5‐HT 1A receptor ligands on rat dorso‐lateral septal neurones in vitro
Author(s) -
Hooff Peter,
Galvan Martin
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.tb14431.x
Subject(s) - spiperone , buspirone , agonist , 8 oh dpat , 5 ht receptor , intrinsic activity , partial agonist , 5 ht1a receptor , chemistry , serotonin agonist , medicine , afterhyperpolarization , receptor , endocrinology , depolarization , pharmacology , biophysics , serotonin , biology , biochemistry
1 The actions of 5‐hydroxytryptamine (5‐HT) and some 5‐HT 1A receptor ligands on neurones in the rat dorso‐lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2 In the presence of tetrodotoxin (1 μ m ) to block any indirect effects, bath application of 5‐HT (0.3–30 μ m ) hyperpolarized the neurones in a concentration‐dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3 The 5‐HT 1A receptor ligands, 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT), N,N‐dipropyl‐5‐carboxamidotryptamine (DP‐5‐CT) and buspirone but not the non‐selective 5‐HT 1 receptor agonist, 1‐m‐trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4 5‐HT, 8‐OH‐DPAT and DP‐5‐CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC 50 s were: DP‐5‐CT 15 n m , 8‐OH‐DPAT 110 n m , 5‐HT 3 μ m and buspirone 110 n m . 5 At a concentration of 3 μ m , the putative 5‐HT 1A receptor antagonists, spiperone, methiothepin, NAN‐190 (1‐(2‐methoxyphenyl)‐4‐[4‐(2‐pthalimido)butyl]piperazine) and MDL 73005EF (8‐[2‐(2,3‐dihydro‐1,4‐benzodioxin‐2‐yl‐methylamino)ethyl]‐8‐azaspiro[4,5]decane‐7,9‐dione methyl sulphonate), produced a parallel rightward shift in the concentration‐response curve to 5‐HT with no significant reduction in the maximum response. The estimated pA 2 values were: NAN‐190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17. 6 The 5‐HT 2 /5‐HT 1C receptor antagonist, ketanserin (3 μ m ) and the 5HT 3 receptor antagonist, tropisetron (3 μ m ) did not antagonize the 5‐HT‐induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization. 7 It is concluded that the 5‐HT‐induced membrane hyperpolarization of rat dorso‐lateral septal neurones is mediated by 5‐HT 1A receptors.