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Central effects induced by MTII following peripheral dosing

, : Central effects induced by MTII following peripheral dosing. Society for Neuroscience Abstracts 26(1-2): Abstract No -77 35

Melanotan-II (MTII) is a cyclic heptapeptide analog of the melanocortin alpha-melanocyte-stimulating hormone (alpha-MSH). Melanocortins have been implicated in several behaviors including grooming, yawning, food intake, and penile erection. These actions are theorized to be through central melanocortin receptors. We have shown erectile behavior in rats following systemic (iv and ip) dosing of MTII (Shadiack et al., 1999). Using a sensitive receptor-binding assay, we have been able to quantify levels of MTII in the cerebral spinal fluid (CSF) at different times after iv dosing. We have also studied the biodistribution of 3H-MTII throughout the rat after iv delivery. In these experiments, a significant amount of radioactivity is detected in the CSF. These studies suggest that a small amount of MTII is able to cross the blood-brain barrier. Published studies by Thiele et al. (1998) have shown that icv administration of MTII caused an activation (increased c-fos expression) of neurons in the paraventricular nucleus of the hypothalamus, the supraoptic nucleus, and central nucleus of the amygdala for example. We treated rats iv with MTII at a dose that elicited penile erection. After a 2-hour survival period, the rats were sacrificed and their brains processed for c-fos immunohistochemistry. Neuronal activation similar to icv injection was observed. In these systemically-dosed rats, c-fos expression increased in autonomic centers of the brain. These data taken together suggest that not only can peripherally dosed MTII cross the blood-brain barrier, but it also can affect functioning in the brain.

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