Factors elevating cAMP attenuate the effects of 8-OH-DPAT on lordosis behavior

The effects of a soluble derivative of forskolin and of two membrane-permeable analogs of cAMP, dibutyryl cAMP, and 8-bromo-cAMP, on the ability of a serotonin (5-HT)(1A) receptor agonist to inhibit lordosis behavior were examined. Sexually receptive, proestrous rats received a bilateral infusion into the ventromedial nucleus of the hypothalamus (VMN) with 68 ng of the forskolin derivative 1, 1.5, 2, or 2.5 h prior to infusion with 200 ng of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Proestrous rats and ovariectomized rats, hormonally primed with 25 microg estradiol benzoate and 500 microg progesterone, were coinfused with 200 ng 8-OH-DPAT and either 50 microg dibutyryl cAMP or 5 microg 8-bromo-cAMP. In proestrous rats, prior infusion with the forskolin derivative reduced the effects of the 5-HT(1A) receptor agonist on lordosis behavior. The best protection occurred at 2 h; by 2.5 h after the preinfusion, any protective effect had disappeared. Coinfusion with either dibutyryl-cAMP or 8-bromo-cAMP reduced the effects of 8-OH-DPAT in proestrous rats. In hormone-primed, ovariectomized rats, dibutyryl cAMP offered significant protection against the effects of 8-OH-DPAT, but there was no protection with 8-bromo-cAMP. These findings are consistent with the speculation that 8-OH-DPAT's inhibition of lordosis behavior results, in part, from an inhibition of adenylyl cyclase, resulting from agonist activation of 5-HT(1A) receptors in the VMN. The findings are also consistent with our earlier observations for differences between proestrous rats and hormone-primed, ovariectomized rats in their response to 5-HT receptor-active compounds.