The role of mu- and delta-opioid receptors in the expression of estrogen -dependent female rat sexual behavior

Abstract

Behavioral and biochemical methods were used to determine the brain region specific role of mu- and delta-opioid receptors (ORs) in the expression of lordosis behavior. Intraventricular (icv) infusion of the highly selective endogenous mu-OR ligands, endomorphin-1 and endomorphin-2, suppressed receptive behavior in ovariectomized (OVX) rats primed with estrogen (E) and progesterone (P). The OR antagonist naloxone blocked endomorphin inhibition of lordosis, confirming that they act through ORs. Site-specific infusion of endomorphins into the medial preoptic area (mPOA) or the ventromedial nucleus of the hypothalamus (VMH) did not suppress lordosis. In contrast, both endomorphins inhibited lordosis when infused into the medial septum/horizontal diagonal band of Broca. The potent mu-OR agonist [D-Ala2-N-MePhe4-Gly 5-ol]-enkephalin (DAMGO) inhibited receptivity after infusion into the VMH or the mPOA, confirming that in these brain regions activation of mu-ORs inhibits lordosis. The OR antagonist naloxone facilitated lordosis after infusion into the mPOA. To investigate whether steroid treatment affects mu-OR coupling to G protein, autoradiographic analysis of DAMGO-stimulated [35S]-GTP-gamma-S binding was used. E alone or with P significantly increased DAMGO-stimulated binding in the mPOA. Therefore, E modulates mu-OR function in a brain-region specific manner. To examine the role of delta-ORs in E facilitation of lordosis we used icv and site-specific infusions of the delta-OR agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) and the selective delta-OR antagonist naltrindole (NTDL). Icv infusion of DPDPE facilitated lordosis behavior, an effect that was reversed by NTDL, confirming that DPDPE facilitation is mediated through delta-ORs. Icv infusion of NDTL transiently but markedly suppressed lordosis behavior. When infused into the VMH DPDPE and NTDL produced facilitation and inhibition of receptivity, respectively. Therefore, delta-ORs might be normally required for E-facilitation of lordosis behavior. Finally, E treatment did not affect delta-OR density in brain regions that regulate reproductive behavior, as assessed by in vitro 3H-DPDPE receptor autoradiography.