Separation of dopaminergic and serotonergic inhibitory mechanisms in the mediation of estrogen-induced lordosis behaviour in the rat

Abstract

The administration of the putative 5-hydroxytrytamine 1 (5-HT 1) agonist 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) (0.0625–1.0 mg·kg −1) suppresses lordosis behaviour induced in ovariectomized female rats by daily treatment for 3–5 days with estradiol benzoate (1.25 μg/rat). A similar suppressive effect on the lordosis behaviour can be obtained by administration of the dopamine/serotonin agonist, lisuride (0.1–0.4 mg·kg −1), or after the administration of the dopamine (DA) agonists, apomorphine (0.2–0.8 mg·kg −1) or quinpirole (0.75–2.50 mg·kg −1. The suppressive effects on the lordosis behaviour by 8-OH-DPAT cannot be antagonized by the DA receptor antagonist haloperidol (0.2 mg·kg −1) neither with methiotepin (0.5 mg·kg −1), which is assumed to be a non-selective 5-HT receptor blocking agent, nor with pirenperone (0.25 mg·kg −1) which is assumed to be a 5-HT 2 receptor blocking agent. However, a partial blockade of the lordosis suppressive effects of 8-OH-DPAT was obtained by treatment with (−)-pindolol, which is thought to be a partial 5-HT 1 blocking agent, suggesting that 8-OH-DPAT exerts its suppressive effects on the lordosis behaviour through the 5-HT system. Haloperidol causes a complete blockade of the suppressive effects of apomorphine and quinpirole suggesting that these drugs exert their inhibitory effects on the lordosis behaviour by activating the DA system. We furthermore found that (−)-pindolol but not haloperidol antagonized the suppressive effect on the lordosis response induced by lisuride suggesting that the lisuride effect was mediated by the 5-HT systems rather than by the DA system. It was concluded that 8-OH-DPAT suppresses lordosis behaviour by activating serotonergic 5-HT 1 receptors.