Effects of D2-dopaminergic receptor stimulation on the lordotic response of female rats

The effects of LY163502, a highly selective D2 dopaminergic agonist, on the lordotic response of ovariectomized, estrogen-treated rats were evaluated. LY163502, administered subcutaneously or orally, produced a significantly greater lordotic response than vehicle. LY175877 [the opposite (+) enantiomer] was found to be inactive. The effects of subcutaneous administered LY163502 were abolished by prior treatment with dopaminergic receptor antagonists such as haloperidol or cis-flupenthixol. These studies are supportive of the view that LY163502 can initiate and potentiate female sexual behavior by stimulating D2 type dopaminergic receptors. In contrast to the enhancement of lordotic response that was observed in nonreceptive female rats, LY163502 was found to have suppressive effects on lordotic response frequency of receptive (estrogen-progesterone-treated) female rats. Reductions in lordotic responding occurred in two dose ranges, above and below the dose range found to potentiate lordotic response. The maximal suppressive effect at the low dose range was observed at 250 pg/kg, SC. This reduction in lordotic responding was proposed to be associated with a selective dopaminergic autoreceptor activation, leading to a diminished dopamine release and expression of a dopamine-mediated behavior (i.e., lordotic response). The reduction of lordotic responding that was observed at higher doses (25 micrograms/kg-25 mg/kg) was associated with an induction of stereotypic behavior that may have disrupted the sexual response pattern.