Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg 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 lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl 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.
KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior
IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.