+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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.

Accession: 034545219

Download citation: RISBibTeXText

Related references

Central administration of the melanocortin agonist MTII fails to amplify the feeding inhibitory actions of peripheral CCK. Society for Neuroscience Abstracts 25(1-2): 534, 1999

Dihydroxyphenylglycol as a Biomarker of Norepinephrine Transporter Inhibition by Atomoxetine: Human Model to Assess Central and Peripheral Effects of Dosing. Journal of Clinical Psychopharmacology 36(6): 675-683, 2016

Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Diabetes 51(5): 1337-1345, 2002

Fluctuations in central and peripheral temperatures induced by intravenous nicotine: central and peripheral contributions. Brain Research 1383: 141-153, 2011

Exercise-induced hyperammonemia: peripheral and central effects. International Journal of Sports Medicine 11(Suppl. 2): S129-S142, 1990

Central infusion of melanocortin agonist MTII in rats: assessment of c-Fos expression and taste aversion. American Journal of Physiology 274(1): R248, 1998

Central administration of MTII suppresses insulin secretion by increased sympathetic drive in ob/ob mice. Society for Neuroscience Abstracts 24(1-2): 1121, 1998

Evaluation of tolerance to the CNS effects of peripheral H-1-antagonist effects of cetirizine and hydroxyzine after multiple dosing. Pharmaceutical Research (New York) 11(10 Suppl. ): S386, 1994

Proof of central effects induced by peripheral administration of cimetidine. Journal de Pharmacologie 11(3): 320-321, 1980

Central infusion of melanocortin agonist MTII reduces voluntary consumption of ethanol in C57BL/6 mice. Alcoholism Clinical and Experimental Research 26(5 Suppl.): 105A, 2002

SHU9119 inhibits MTII, but not dexfenfluramine induced anorexia. Society for Neuroscience Abstracts 25(1-2): 618, 1999

Central and peripheral effects of lithium on amphetamine-induced hyperactivity in rats. Pharmacology Biochemistry and Behavior 14(4): 439-442, 1981

Tachykinin induced regional gastric motility changes peripheral and central effects. Digestive Diseases and Sciences 30(8): 758, 1985

Effects of central and peripheral morphine on trh induced increases in intestinal transit. Digestion 46(Suppl. 1): 42-43, 1990

Pharmacoeconomic evaluation of dosing vecuronium by peripheral nerve stimulation vs standard clinical dosing in critically ill patients. Pharmacotherapy 16(3): 508-509, 1996