5-HT1A receptor antagonists and lordosis behavior

• Published in: Neuropharmacology Vol. 35; no. 4; pp. 489 - 496
• Main Authors: UPHOUSE, L, ANDRADE, M, CALDAROLA-PASTUSZKA, M, JACKSON, A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.04.1996
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Behavioral psychophysiology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Hypothalamus, Middle; Infusions, Parenteral; Neurotransmission and behavior; Ovariectomy; Ovary - physiology; Pindolol - pharmacology; Piperazines - pharmacology; Posture; Propranolol - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Inbred Strains; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Sexual Behavior, Animal - drug effects; Vertebrata; Mammalia; Rat; Animal; Ventromedial nucleus; Rodentia; Sexual behavior; Female; Lordosis; Hypothalamus; Diencephalon; 5-HT1A receptor
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(95)00196-4

In proestrous rats, serotonin 1A (5-HT1A) receptor agonists inhibit lordosis behavior within 5-15 min following infusion into the ventromedial nucleus of the hypothalamus (VMN). In the present report, the lordosis-inhibiting effects of the 5-HT1A agonist [(+/-) 8-hydroxy-2- (di-n-propylamino) tetralin) (8-OH-DPAT] were shown to be attenuated with 5-HT1A receptor antagonists. Two compounds, propranolol and pindolol, that function as both beta-adrenergic and 5-HT1A receptor antagonists, and (+) WAY100135 (chiral N-t-butyl-3-(1-(4-(2-methoxy) phenyl)piperazinyl)-1-phenylpropionamide dihydrochloride, quarter hydrate), a more selective 5-HT1A receptor antagonist, were found to reduce the lordosis-inhibiting effects of 8-OH-DPAT infusion into the VMN. Proestrous rats were co-infused into the VMN with 200 ng 8-OH-DPAT plus 1000 ng or 2000 ng pindolol, 1000 ng or 2000 ng propranolol, or 2000 ng (+) WAY100135. Co-infusion with 1000 ng or 2000 ng pindolol attenuated the inhibitory effects of 8-OH-DPAT; co-infusion of 1000 ng, but not 2000 ng, propranolol, reduced the effects of 8-OH-DPAT; and co-infusion with 2000 ng (+) WAY100135 attenuated the effects of 8-OH-DPAT. Bilateral VMN infusion with 2500 ng (+) WAY100135 facilitated lordosis behavior in suboptimally, hormone-primed ovariectomized rats. These findings strengthen the argument that the inhibitory effect of 5-HT1A receptor agonists on lordosis behavior is the result of their activation of VMN 5-HT1A receptors.