Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist - PubMed (original) (raw)

Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist

James G Pfaus et al. Proc Natl Acad Sci U S A. 2004.

Abstract

Disorders of sexual desire affect an estimated 30% of women in North America and Europe, with etiologies based on interpersonal, personal, and physiological factors. There are currently no pharmacological agents approved for use in the treatment of female sexual dysfunction. This is due, in part, to a focus on the effects of experimental drugs on reflexive components of sexual behavior, such as lordosis, in animal models. Here we report that PT-141, a peptide analogue of alpha-melanocyte-stimulating hormone that binds to central melanocortin receptors, selectively stimulates solicitational behaviors in the female rat. This occurs without affecting lordosis, pacing, or other sexual behaviors. PT-141 did not cause generalized motor activation, nor did it affect the perception of sexual reward. A selective pharmacological effect on appetitive sexual behavior in female rats has not been reported previously, and indicates that central melanocortin systems are important in the regulation of female sexual desire. Accordingly, PT-141 may be the first identified pharmacological agent with the capability to treat female sexual desire disorders.

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Figures

Fig. 1.

Fig. 1.

Pacing chambers used to assess female sexual behavior in the present experiments. (Upper) Copulation in bilevel chambers, initiated by solicitation (1), followed by anogenital investigation of the female (2), a runaway by the female to the other level (3), enticing the male to chase her, and finally the display of lordosis by the female (4), which allowed the male to mount with vaginal intromission. (Lower) Copulation in unilevel pacing chambers. The female on the left is crawling through a hole in a central partition to initiate copulation with the male. The female on the right has just been mounted.

Fig. 2.

Fig. 2.

Dose–response effects of PT-141 on sexual behavior in bilevel chambers. (Top) Effects on solicitations in females primed with estrogen and progesterone (E+P) or estrogen alone (E alone). For E+P-treated females, _F_3,35 = 3.73, P < 0.02. For females treated with E alone, _F_1,37 = 5.52, P < 0.03. Post hoc tests revealed that both the 100- and 200-μg/kg doses increased the number of solicitations significantly compared to saline-treated controls (P values < 0.05). (Middle) Effects on pacing in females primed with E+P or E alone. (Bottom) Effects on lordosis quotients in females primed with E+PorE alone. Data are means + SEM. *, P < 0.05 from control.

Fig. 3.

Fig. 3.

Dose–response effects of PT-141 on the sexual behavior of E+P-primed female rats in unilevel pacing chambers. (Top Left) Effects on solicitations (_F_3,34 = 6.62, P < 0.002). (Top Right) Effects on hops and darts (_F_3,34 = 4.12, P < 0.02). Post hoc tests revealed that both the 100- and 200-μg/kg doses increased solicitation and hops and darts significantly (P values < 0.05). (Middle Left) Effects on lordosis quotients. (Middle Right) Effects on female mounting of the male (FMM). _F_3,34 = 3.84, P < 0.02. Post hoc tests revealed a significant effect of the highest dose only (P < 0.05). (Bottom Left) Effects on the intromission return latency. (Bottom Right) Effects on the ejaculation return latency). _F_3,34 = 3.65, P < 0.02. Post hoc tests revealed a significant effect of the 100- and 200-μg/kg doses (P values < 0.05) Data are means ± SEM. *, P < 0.05 from control.

Fig. 4.

Fig. 4.

Effects of PT-141 or saline on locomotion and CPP. (Upper) Effects of saline or PT-141 (200 μg/kg) on the number of grid crossings in an open field during a 15-min test of locomotor activity. (Lower) Effects of PT-141 or saline on CPP induced by sequential paring of copulation in the one-hole versus four-hole condition. Data are means + SEM. *, P < 0.05 from pretest.

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