In the ventral tegmental area, the membrane-mediated actions of progestins for lordosis of hormone-primed hamsters involve phospholipase C and protein kinase C

Abstract

Progestin-facilitated lordosis of rodents is enhanced by activation of dopamine type 1 (D(1)) or GABA(A) receptors, their downstream G-proteins, and/or second messengers in the ventral tegmental area (VTA). We examined whether the ability of progestins to enhance lordosis via actions at D(1) and/or GABA(A) receptors is contingent upon activation of the second messenger phospholipase C (PLC) and its associated kinase, protein kinase C (PKC), in the VTA. If the actions of progestins through D(1) and GABA(A) receptors in the VTA are mediated through PLC and PKC, then inhibiting PLC formation (Experiment 1) or blocking PKC (Experiment 2) should reduce progestin-facilitated lordosis and its enhancement by D(1) (SKF38393) or GABA(A) (muscimol) receptor agonists. In Experiment 1, ovariectomised hamsters, primed with oestradiol (10 microg; h 0) + progesterone (100 microg; h 45), were pretested for lordosis and motor behaviour (h 48) and then infused with the PLC inhibitor, U73122 (400 nM/side), or vehicle. Thirty minutes later, hamsters were retested and then received infusions of SKF38393 (100 ng/side), muscimol (100 ng/side), or vehicle to the VTA. Hamsters were post-tested for lordosis and motor behaviour 30 min later. In Experiment 2, a similar protocol was utilised except that instead of the PLC inhibitor hamsters were infused with the PKC inhibitor, bisindolylmaleimide (75 nM/side). Systemic progesterone, SKF38393-, and muscimol-facilitated lordosis was attenuated by infusion of the PLC inhibitor, U73122, or the PKC inhibitor, bisindolylmaleimide, compared to vehicle to the VTA. Thus, the actions of progestins in the VTA to enhance lordosis through D(1) and/or GABA(A) may include downstream activity of PLC and PKC.