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.
Uphouse
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L
Department of Biology, Texas Woman's University, Denton, TX 76204, USA.
Maswood
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S
Jackson
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D010052:Ovariectomy; D011187:Posture / Q000502:physiology*; D011359:Proestrus / Q000502:physiology; D011374:Progesterone / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D005576:Colforsin; C074283:estradiol 3-benzoate; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D004958:Estradiol; D003994:Bucladesine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP