Protein kinase inhibitors infused intraventricularly or into the ventromedial hypothalamus block short latency facilitation of lordosis by oestradiol

Abstract

| INTRODUC TI ONIn ovariectomised (OVX) rats, lordosis behaviour can be induced by repeated or high doses of oestradiol (E 2 ) without subsequent treatment with progesterone. 1-8 Moreover, intracerebral or subcutaneous administration of E 2 induces lordosis behaviour with a short latency in E 2 -benzoate (EB) primed rats. 9-12 Despite the great variety of physiological and reproductive effects of oestrogens, the cellular Abstract An injection of unesterified oestradiol (E 2 ) facilitates receptive behaviour in E 2 benzoate (EB)-primed, ovariectomised female rats when it is administered i.c.v. or systemically. The present study tested the hypothesis that inhibitors of protein kinase A (PKA), protein kinase G (PKG) or the Src/mitogen-activated protein kinase (MAPK) complex interfere with E 2 facilitation of receptive behaviour. In Experiment 1, lordosis induced by i.c.v. infusion of E 2 was significantly reduced by i.c.v. administration of Rp-cAMPS, a PKA inhibitor, KT5823, a PKG inhibitor, and PP2 and PD98059, Src and MAPK inhibitors, respectively, between 30 and 240 minutes after infusion. In Experiment 2, we determined whether the ventromedial hypothalamus (VMH) is one of the neural sites at which those intracellular pathways participate in lordosis behaviour induced by E 2 . Administration of each of the four protein kinase inhibitors into the VMH blocked facilitation of lordosis induced by infusion of E 2 also into the VMH.These data support the hypothesis that activation of several protein kinase pathways is involved in the facilitation of lordosis by E 2 in EB-primed rats.