PT-141 Peptide (10MG)

This 2004 study in the Proceedings of the National Academy of Sciences (Pfaus et al., Concordia University) tested PT-141 in hormone-primed, ovariectomized female rats. Behavioral neuroscience divides female rat sexual behavior into appetitive behaviors, such as solicitations and hops and darts, and receptive behaviors, such as the lordosis posture. The researchers asked whether PT-141 changes one category without changing the other.

They also tested whether PT-141 changed general movement in an open field, or the conditioned place preference that rats develop for a chamber linked to paced mating.

Scope: This was a behavioral study in female rats. It did not test PT-141 in people.

• Citation: Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P. Proc Natl Acad Sci USA. 2004;101(27):10201–10204.
• Animals: Ovariectomized female Long-Evans rats, primed with estradiol plus progesterone, or estradiol alone
• Groups: 40 rats (bilevel chambers, estradiol plus progesterone), 20 (bilevel, estradiol alone), 40 (unilevel chambers), 20 (open field) and 20 (place preference)
• Administration in the study: Subcutaneous, 5 minutes before each test, compared with saline
• Measurements: Solicitations, hops and darts, pacing, lordosis quotient, female mounting, return latencies, locomotion, conditioned place preference
• Funding and disclosure: Palatin Technologies, which manufactures PT-141, provided financial support. Two authors owned Palatin stock.

Many earlier pharmacology studies of female rat sexual behavior focused on lordosis, a reflexive posture. The authors argued that this focus misses the appetitive behaviors female rats use to initiate and pace contact. Central melanocortin receptors, especially MC3 and MC4, are expressed in hypothalamic and limbic regions involved in motivated behavior.

This study used PT-141 as a pharmacological tool to examine whether activating these receptors selectively changes appetitive measures.

Females were ovariectomized and primed with estradiol benzoate plus progesterone, or estradiol alone. Each received 10 preliminary sexual-behavior tests before the experiment. In the main experiments, rats received PT-141 at 0 (saline), 50, 100 or 200 µg/kg. The estradiol-alone group received only 0 or 200 µg/kg. These amounts describe the published rat protocol only.

The researchers used two testing set-ups:

• Bilevel chambers: The female can solicit the male, run to another level and pace contact. Researchers scored solicitations, hops and darts, pacing, rejections and lordosis quotients over 30 minutes.
• Unilevel pacing chambers: A divider with small holes lets only the female cross. Researchers scored the same behaviors, plus female mounting and return latencies after mounts, intromissions and ejaculation.

Separate groups were tested for locomotion in an open field and for conditioned place preference linked to paced mating.

In rats primed with estradiol plus progesterone, PT-141 at 100 and 200 µg/kg significantly increased the number of solicitations compared with saline. The 200 µg/kg dose also increased solicitations in rats primed with estradiol alone.

PT-141 did not change pacing, lordosis quotients or the other behaviors scored in the bilevel chambers.

In unilevel chambers, PT-141 significantly increased both solicitations and hops and darts, but not lordosis. Rats given the highest dose also showed more female mounting of the male.

Return latencies after mounts and intromissions did not change. Return latency after ejaculation, which is normally longer, increased further with PT-141.

PT-141 at 200 µg/kg did not increase grid crossings in an open field, so the behavioral changes were not explained by a general increase in activity. PT-141 also did not alter the normal development of conditioned place preference for paced mating. The authors interpreted this as no change in the rewarding properties of paced copulation in this paradigm.

PT-141 binds melanocortin receptor subtypes 1, 3 and 4. The authors proposed that the behavioral effects most likely involve MC3 and MC4 receptors in the central nervous system. This was an interpretation: the study did not identify the brain regions or receptor subtypes involved, and it did not rule out peripheral actions.

• The study used ovariectomized, hormone-primed rats, which is a specific experimental model of female rat sexual behavior.
• Results depended on the testing set-up and hormone priming, with clearer effects in unilevel chambers.
• Group sizes were moderate (20–40 rats per experiment), and some measures were tested at only one dose.
• The manufacturer of PT-141 funded the study, and two authors held stock in the company.
• Rat behavioral measures do not establish effects, safety or dosing in other species, including people.

Pfaus et al. (2004) reported that PT-141 increased appetitive measures in hormone-primed female rats, including solicitations, hops and darts, and, at the highest dose, female mounting. Lordosis, pacing, general locomotion and conditioned place preference did not change. The authors linked these behavior-specific effects to central melanocortin receptor activation.

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