In the ventral tegmental area (VTA),
progestins facilitate
lordosis via rapid actions at membrane
dopamine Type 1-like (D(1)) and/or
GABA(A) receptors (
GBRs), rather than via cognate, intracellular
progestin receptors (PRs). Downstream signal transduction pathways involved in these effects were investigated using
lordosis as a bioassay. If
progestins' actions at D(1) and/or
GBRs in the VTA require activation of
G-proteins,
adenylyl cyclase,
cyclic AMP-dependent protein kinase A (PKA),
phospholipase C (PLC), and/or PKC, then pharmacologically blocking these pathways would be expected to attenuate
progestin-facilitated
lordosis and its enhancement by D(1) and GBR activity. Ovariectomized,
estradiol-primed rats were infused first with vehicle or signal transduction inhibitor, and second with vehicle, a D(1) or GBR agonist, and then with vehicle or
progestins to the VTA. Rats were tested for
lordosis following infusions. Results indicated that initiation of
G-proteins,
adenylyl cyclase, PKA, PLC, or PKC in the VTA is required for rapid effects of
progestins through D(1) and/or
GBRs to facilitate
lordosis. As well,
progestins' actions at
n-methyl-d-aspartate receptors (NMDARs) may modulate activity at D(1) and/or
GBRs and
mitogen activated protein kinase (MAPK) may be a common signaling pathway. Findings from a microarray study demonstrated that there was upregulation of genes associated with
steroid metabolism,
GBRs, D(1), NMDARs and signal transduction factors in the midbrain VTA of naturally receptive mated compared to non-mated rats. Thus, in the VTA,
progestins have rapid membrane-mediated actions via D(1),
GBRs, NMDARs and their downstream signal transduction pathways.