5-HT1A receptor antagonists and lordosis behavior

Abstract

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.