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

Abstract

Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10 μg estradiol benzoate and 500 μg 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 μl 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.