The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior.

Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10 microg estradiol benzoate and 500 microg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT(2) receptor agonist, (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosis-inhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10(-5) nmol in a 0.5 microl infusion volume was effective and there was little evidence of dose responsivity between 10(-5) and 10(-1) nmol of BIM. In contrast, prior infusion with vehicle or with 10(-7) nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior.

Mild restraint reduces the time hormonally primed rats spend with sexually active males.

The effect of 5 min of restraint on the time sexually-receptive females spend in the compartment of a sexually active male was examined. Ovariectomized females, hormonally primed with 10 microg estradiol benzoate and 500 microg progesterone (EP) or primed only with estradiol benzoate (EO) were used. After the restraint or home-cage experience, females were tested for 30 min in a chamber that allowed the female to escape to a small "burrow". Females, subjected to restraint, left the male's compartment faster and spent significantly less time in the male's compartment than did non-restrained females. This was true for both EP and EO females. When females were injected with the 5-HT(2B/2C)-receptor antagonist, SB 206553, 15 min before restraint, time spent in the male's compartment was even further reduced. However, additional studies indicated that it was the stress of the injection rather than the action of the drug that was responsible for the female's behavior. These findings are discussed in terms of their significance to the understanding of the female's reproductive response to stress and are compared to prior findings, where lordosis behavior was significantly reduced by restraint.