Activity of protein kinase C is important for 3alpha,5alpha-THP's actions at dopamine type 1-like and/or GABAA receptors in the ventral tegmental area for lordosis of rats

Abstract

In the ventral tegmental area, progestogens facilitate sexual receptivity of rodents via actions at dopamine type 1-like and/or gamma-aminobutyric acid type A receptors and activation of downstream signal transduction molecules. In the present study, we investigated whether effects of progesterone's metabolite, 3alpha,5alpha-THP, to enhance lordosis via actions at these receptors in the ventral tegmental area requires phospholipase C-dependent protein kinase C. The objective of this study was to test the hypothesis that: if progestogens' actions through dopamine type 1-like and/or gamma-aminobutyric acid type A receptors in the ventral tegmental area for lordosis require protein kinase C, then inhibiting protein kinase C in the ventral tegmental area should reduce 3alpha,5alpha-THP-facilitated lordosis and its enhancement by dopamine type 1-like or gamma-aminobutyric acid type A receptor agonists. Ovariectomized, estradiol (E(2); 10 microg s.c. at h 0)-primed rats were tested for their baseline lordosis responses and then received a series of three infusions to the ventral tegmental area: first, bisindolylmaleimide (75 nM/side) or vehicle; second, SKF38393 (100 ng/side), muscimol (100 ng/side), or vehicle; third, 3alpha,5alpha-THP (100, 200 ng/side) or vehicle. Rats were pre-tested for lordosis and motor behavior and then tested for lordosis after each infusion and 10 and 60 min after the last infusion. Rats were tested for motor behavior following their last lordosis test. As has been previously demonstrated, 3alpha,5alpha-THP infusions to the ventral tegmental area increased lordosis and effects were further enhanced by infusions of SKF38393 and muscimol. Infusions of bisindolylmaleimide to the ventral tegmental area attenuated 3alpha,5alpha-THP-, SKF38393-, and/or muscimol-facilitated lordosis. Effects on lordosis were not solely due to changes in general motor behavior. Thus, 3alpha,5alpha-THP's actions in the ventral tegmental area through membrane receptors may require activity of protein kinase C.

Figure 1. SKF38393- or muscimol-mediated increases in 3α,5α-THP-facilitated lordosis of E₂-primed rats are attenuated by infusions of the PKC inhibitor, bisindolylmaleimide (BIS), to the VTA

Figure depicts lordosis quotients (LQs) of E₂-primed rats, 60 minutes following 3α,5α-THP infusions, and pretreatment with vehicle or BIS pre-treatment, and vehicle (open), SKF38393 (stippled), or muscimol (solid) at each 3α,5α-THP dosage (0, 100 or 200 ng). One asterisk above bars indicates significantly lower LQs due to BIS infusion (p<0.05) vs. vehicle infusions at that 3α,5α-THP dosage. Two asterisks indicates significantly increased LQs due to agonist infusions (p<0.05) vs. vehicle infusions at that 3α,5α-THP dosage. # indicates significantly increased LQs due to 3α,5α-THP infusions (p<0.05) vs. vehicle infusions.