18-Methoxycoronaridine: a potential new treatment for obesity in rats?
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Excessive eating often leads to obesity. Although a variety of neurotransmitters and brain regions are involved in modulating food intake, a role of accumbal dopamine is thought to be critical for several aspects of this behavior. Since 18-methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, was previously shown to alter dopamine release in the nucleus accumbens in response to chronic injections of cocaine and morphine, this drug could be a promising therapy for abnormal eating behavior.
Assess the effect of 18-MC on the consumption of sucrose (15%) vs. water in a self-administration paradigm and on the intake of freely available palatable fluids (i.e., 5% sucrose, 0.1% saccharin, and 0.6% saline solutions) as well as on water intake. Determine whether repeated administration of 18-MC (20 mg/kg i.p.) affects weight gain, food intake, and fat deposition in rats drinking 30% sucrose solution.
Acute administration of 18-MC (10–40 mg/kg i.p.) reduced operant responding for sucrose and decreased ad libitum ingestion of sucrose, saccharin, and saline. The highest dose of 18-MC also reduced consumption of water when palatable fluids were not available. In rats having unlimited access to sucrose (30%), chronic treatment with 18-MC (20 mg/kg i.p.) prevented sucrose-induced increases in body weight, decreased fat deposition, and reduced consumption of sucrose while not altering food intake.
These data suggest that antagonism of α3β4 nicotinic receptors may be involved in the regulation of intake of palatable substances regardless of its caloric value and may participate in maintaining obesity.
KeywordsPalatable fluids Feeding behavior Nicotinic receptors Obesity
This study was supported by NIDA grant DA016283. The authors would like to thank Michael Bryda for the technical assistance.
- Blaha V, Yang ZJ, Meguid M, Chai JK, Zadak Z (1998) Systemic nicotine administration suppresses food intake via reduced meal sizes in both male and female rats. Acta Medica (Hradec Kralove) 41:167–173Google Scholar
- Glick SD, Maisonneuve IM, Kuehne ME, Bandarage UK (1999) (±)18-Metoxycoronaridine: a novel iboga alkaloid congener having potential anti-addictive efficacy. CNS Drug Rev 5(1):27–42 (Neva Press, Branford, CT)Google Scholar
- Greenhalgh CE, Smith JW, Clifton PG (2008) WO03/062224 is an in vivo selective agonist at nicotinic beta4 receptors. Pharmacol Biochem Behav (in press)Google Scholar
- Guide for the Care and Use of Laboratory Animals (1996). Institute of Laboratory Animal Resources Commission for Life Sciences, National Research Council. National Academy Press, Washington, D.C.Google Scholar
- Jerlhag E, Egecioglu E, Dickson SL, Svensson L, Engel JA (2008) Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. Eur Neuropsychopharmacol 18:508–518PubMedCrossRefGoogle Scholar