Effect of serotonin 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the prolactin response to restraint and ether stress.
Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT1, 5-HT2 or 5-HT3 receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT1 + 2 receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT2 receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT1, 5-HT2 as well as 5-HT3 receptors.
Jørgensen
H
H
Department of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Knigge
U
U
Warberg
J
J
D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D004986:Ether / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012702:Serotonin Antagonists; D013312:Stress, Physiological / Q000139:chemically induced*; D000077526:Tropisetron
D004873:Ergolines; D007211:Indoles; D012702:Serotonin Antagonists; D004986:Ether; D017294:Ondansetron; D000077526:Tropisetron; D011388:Prolactin; D007650:Ketanserin; C032663:LY 53857; D008784:Methysergide