Anti-sense oligonucleotides, for progestin receptors in the VMH and glutamic acid decarboxylase in the VTA, attenuate progesterone-induced lordosis in hamsters and rats

Immunocytochemical (ICC) staining for progesterone (P) receptors (PRs) and glutamic acid decarboxylase (GAD), the enzyme responsible for GABA producti on, reveal that there are many PRs in the ventral medial hypothalamus (VMH) and many GAD containing neurons in the ventral tegmental area (VTA). To in vestigate P's action on lordosis in the VMH and VTA, anti-sense oligos spec ific to PRs and GAD(65+67) were intracerebrally infused into the VMH and VT A of 24 ovariectomized hamsters and 40 ovariectomized rats. Estradiol benzo ate (2 mu g) primed hamsters and rats were infused to the VMH and the VTA w ith either PR (250 ng/1.0 mu l infusion) or GAD (500 ng/1.0 mu l infusion) anti-sense oligos, their scramble controls, or saline Vehicle at hour 0 and again at hour 24. At hr 44, rodents were subcutaneously injected with P (5 00 mu g) and were tested for sexual receptivity with a male 4 h later. Ther e were significant reductions in lordosis of hamsters and rats following PR anti-sense infusions to the VMH compared to scrambled or Vehicle control i nfusions. Effects of PR anti-sense to the VMH were not different from combi ned VMH and VTA PR anti-sense infusions; however, VMH infusions reduced lor dosis compared to VTA-only anti-sense infusions. GAD anti-sense infusions r educed lordosis when infused into the VTA, compared to scrambled or saline vehicle infusions. Lordosis responsiveness following VTA GAD anti-sense inf usions was not different from combined VMH and VTA infusions, but VTA infus ions of GAD anti-sense reduced lordosis compared to VMH-only anti-sense inf usions. These data suggest that in the VMH, PRs are important for P-facilit ated lordosis, whereas in the VTA, GABAergic neurons may be an important su bstrate for mediating P's actions on lordosis of rodents. (C) 2000 Elsevier Science B.V. All rights reserved.