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Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5‐HT 1A and 5‐HT 1B receptor agonists 8‐OH‐DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD‐299 and NAS‐181
Author(s) -
Hillegaart Viveka,
Ahlenius Sven
Publication year - 1998
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 - 10.1038/sj.bjp.0702239
Subject(s) - agonist , endocrinology , medicine , chemistry , antagonist , 5 ht receptor , receptor , 5 ht1a receptor , receptor antagonist , pharmacology , metergoline , serotonin , biology
Ejaculatory problems and anorgasmia are well‐known side‐effects of the SSRI antidepressants, and a pharmacologically induced increase in serotonergic neurotransmission inhibits ejaculatory behaviour in the rat. In the present study the role of 5‐HT 1A and 5‐HT 1B receptors in the mediation of male rat ejaculatory behaviour was examined by use of selective agonists and antagonists acting at these 5‐HT receptor subtypes. The 5‐HT 1A receptor agonist 8‐OH‐DPAT (0.25–4.00 μmol kg −1 s.c.) produced an expected facilitation of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the new selective 5‐HT 1A receptor antagonist ( R )‐3‐ N,N ‐dicyclobutylamino‐8‐fluoro‐3,4‐dihydro‐2 H ‐1‐benzopyran‐5‐carboxamide hydrogen (2 R ,3 R ) tartrate monohydrate (NAD‐299) (1.0 μmol kg −1 s.c.). NAD‐299 by itself (0.75–3.00 μmol kg −1 s.c.) did not affect the male rat ejaculatory behaviour. The 5‐HT 1B receptor agonist anpirtoline (0.25–4.00 μmol kg −1 s.c.) produced a dose‐dependent inhibition of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the 5‐HT 1B receptor antagonist isamoltane (16 μmol kg −1 s.c.) as well as by the new and selective antagonist ( R )‐(+)‐2‐(3‐morpholinomethyl‐2 H ‐chromene‐8‐yl)oxymethylmorpholino methansulphonate (NAS‐181) (16 μmol kg −1 s.c.). Isamoltane (1.0–16.0 μmol kg −1 s.c.) and NAD‐181 (1.0–16.0 μmol kg −1 s.c.) had no, or weakly facilitatory effects on the male rat ejaculatory behaviour. The non‐selective 5‐HT 1 receptor antagonist (−)‐pindolol (8 μmol kg −1 s.c.), did not antagonize the inhibition produced by anpirtoline. The present results demonstrate opposite effects, facilitation and inhibition, of male rat ejaculatory behaviour by stimulation of 5‐HT 1A and 5‐HT 1B receptors, respectively, suggesting that the SSRI‐induced inhibition of male ejaculatory dysfunction is due to 5‐HT 1B receptor stimulation.