Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist.
Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight. Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. In addition, after mapping the binding sites for [(3)H]SNAP-7941 in rat brain, we evaluated its effects in a series of behavioral models. SNAP-7941 produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may be useful not only in the management of obesity but also as a treatment for depression and/or anxiety.
Borowsky
Beth
B
Synaptic Pharmaceutical Corporation, Paramus, New Jersey, USA.
Durkin
Margaret M
MM
Ogozalek
Kristine
K
Marzabadi
Mohammad R
MR
DeLeon
John
J
Lagu
Bharat
B
Heurich
Rainer
R
Lichtblau
Harvey
H
Shaposhnik
Zoya
Z
Daniewska
Irena
I
Blackburn
Thomas P
TP
Branchek
Theresa A
TA
Gerald
Christophe
C
Vaysse
Pierre J
PJ
Forray
Carlos
C
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001067:Appetite Depressants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D004032:Diet; D004435:Eating / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007028:Hypothalamic Hormones / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010880:Piperidines / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001067:Appetite Depressants; D007028:Hypothalamic Hormones; D008543:Melanins; D010880:Piperidines; D010907:Pituitary Hormones; D011743:Pyrimidines; D011979:Receptors, Pituitary Hormone; C464854:SNAP7941; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone