Centrally administered MTII affects feeding, drinking, temperature, and activity in the Sprague-Dawley rat.
MTII, an agonist of melanocortinergic receptors, is a well-documented anorexigenic agent in rats. Many investigators have reported its effects on feeding without considering concurrent alterations in other behaviors. Accordingly, we performed studies to simultaneously measure nocturnal feeding, drinking, activity, and temperature of rats after intracerebroventricular (third ventricle) administration of a wide dose range of MTII (0.05-500 ng). We observed that MTII modulates these physiological parameters in a dose-dependent manner. Low doses of MTII (0.05 ng) caused reductions in feeding without alterations in body temperature, drinking, or activity. In contrast, hyperthermia and disrupted drinking patterns, along with food intake reductions, were evident at doses exceeding 50 ng. The fact that low doses altered only feeding, whereas higher doses affected a range of parameters, suggests that certain melanocortin-induced behavioral changes may be mediated by distinct populations of melanocortin receptors with varying affinities or that those changes seen at higher doses may be nonspecific in nature.
Murphy
B
B
Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA. beth_murphy@merck.com
Nunes
C N
CN
Ronan
J J
JJ
Hanaway
M
M
Fairhurst
A M
AM
Mellin
T N
TN
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D004327:Drinking Behavior / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D008991:Monitoring, Physiologic; D009043:Motor Activity / Q000187:drug effects*; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020542:Third Ventricle; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D000521:alpha-MSH