Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior

Abstract

Ovariectomized rats were hormonally primed with 10 μg estradiol benzoate or with estradiol benzoate plus 500 μg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT 1B/1D receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1′-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females that had experienced minimal handling between ovariectomy and use in the experiment, infusion with the water vehicle transiently inhibited lordosis behavior, and the 5-HT 1B/1D receptor antagonist amplified this inhibition. There were no effects in rats hormonally primed with estrogen and progesterone. Handling for two days before the experiment reduced the effects of the infusions in estrogen-primed rats. However, when a 5 min restraint experience followed infusion with GR 127935, there was a significant decline in lordosis behavior that persisted for 10 to 15 min after the experience. Regardless of the prior experience or type of infusion, the addition of progesterone to the hormonal priming completely prevented the lordosis inhibition. These findings are consistent with prior evidence that progesterone protects against the inhibitory effects of a 5 min restraint experience on lordosis behavior. Moreover, these are the first experiments to demonstrate an inhibitory effect of a selective 5-HT 1B/1D receptor antagonist in the VMN on lordosis behavior of estrogen primed, but not estrogen and progesterone primed, ovariectomized rats.

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists

“…Instead of further confirming the importance of the 5-HT 1A receptor, we tried to block the paroxetine effects on female rat sexual behaviors with the 5-HT 1B antagonist GR125,743. The rationale for that was that 5-HT 1B agonists inhibit lordosis in female rats (Uphouse et al 2009), particularly when endogenous 5-HT release is heightened by stress . A heightened 5-HT release is exactly what is associated with SSRI treatment, and we reasoned that antagonism of the 5-HT 1B receptor might enhance female sexual behaviors after a paroxetine-induced reduction.…”

Pharmacology of serotonin and female sexual behavior

“…MBH infusion with the 5-HT 1B/1D receptor antagonist, GR 127935 N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3--yl)-1,1′-biphenyl-4-carboxamide hydrochloride (Liao et al, 2000), inhibited lordosis behavior in rats made sexually receptive with estradiol benzoate priming but was considerably less evident in rats hormonally primed with estradiol benzoate and progesterone (Uphouse et al, 2009). Interestingly, the effect of the 5-HT 1B/1D receptor antagonist appeared to result from an amplification of infusion stress on lordosis behavior (Uphouse et al, 2009).…”

“…Interestingly, the effect of the 5-HT 1B/1D receptor antagonist appeared to result from an amplification of infusion stress on lordosis behavior (Uphouse et al, 2009). After infusion with the 5-HT 1B/1D receptor agonist, CP 93129 [1,4-dihydro-3-(1,2,3,6-tetrahydro-4- 27 pyridinyl)-5H-pyrrol[3,2-bi]pyridin-5-one-dihydrochloride] (Uphouse et al, 2010), rats primed only with estradiol benzoate showed lordosis inhibition, but in contrast to a transient decline in lordosis behavior following infusion with the antagonist, effects of CP 93129 were long lasting.…”

Progesterone reduces the inhibitory effect of a serotonin 1B receptor agonist on lordosis behavior

“…In early studies with nonselective 5-HT 1B receptor compounds, a facilitative role for 5-HT 1B receptors was suggested (Aiello-Zaldivar et al, 1992; Mendelson and Gorzalka, 1990). In support of this possibility, infusion of a selective 5-HT 1B receptor antagonist, GR 127935, into the VMN amplified the negative effects of 5 min restraint on lordosis behavior of estradiol benzoate-primed ovariectomized rats (Uphouse et al, 2009). …”

“…Fischer rats have been reported to show evidence of high emotionality in a variety of behavioral tests (Dhabhar et al, 1993; Izumi et al, 1996; Rosecrans et al, 1986; Stohr et al, 2000) and show a larger hypothalamic-pituitary-adrenal response to stress than several other rat strains (Armario et al, 1995; Dhabhar et al, 1995; Gomez-Serrano et al, 2009; Marissal-Arvy et al, 2007; Rosecrans et al, 1986; Sarrieau and Mormede, 1998). Lordosis behavior of estradiol benzoate-primed Fischer females is also vulnerable to disruption by a mild stress (Truitt et al, 2003; Uphouse et al, 2009; White and Uphouse, 2004). In prior experiments, we have shown that a stressor as mild as 5 min of restraint can substantially reduce lordosis behavior of EO Fischer rats while having no effect in EP rats (Truitt et al, 2003).…”