Abstract
Rationale
18-Methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, has been previously shown, in rats, to reduce the self-administration of several drugs of abuse, reduce operant responding for sucrose, and prevent the development of sucrose-induced obesity. It has become increasingly apparent that there is a significant overlap between the systems regulating drug reward and food intake, therefore, we investigated whether 18-MC might modulate the effects of ghrelin, one of several orexigenic peptides recently implicated in both feeding and drug reward.
Objectives
In female Sprague–Dawley rats, we determined whether acute 18-MC treatment would reduce both ghrelin-induced increases in sucrose intake and ghrelin-elicited increases in accumbal dopamine levels.
Results
Pretreatment with 18-MC (20 mg/kg, i.p.), given prior to the administration of ghrelin (1 μg, lateral ventricle), blocked ghrelin-induced increases in sucrose (5%) intake in a two-bottle open access paradigm. Using in vivo microdialysis, 18-MC (both 20 and 40 mg/kg) prevented ghrelin (2 μg, intraventral tegmental area)-induced increases in extracellular dopamine in the nucleus accumbens. 18-MC had no effect on deposition of fat or on serum levels of glucose, triglycerides, and cholesterol in ghrelin-treated rats.
Conclusions
The present results suggest that one potential mechanism by which 18-MC exerts its effects on palatable food consumption is via modulation of ghrelin’s effects.
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Acknowledgments
This study was supported by DA 016283.
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Sarah E. McCallum and Olga D. Taraschenko contributed equally to this work.
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McCallum, S.E., Taraschenko, O.D., Hathaway, E.R. et al. Effects of 18-methoxycoronaridine on ghrelin-induced increases in sucrose intake and accumbal dopamine overflow in female rats. Psychopharmacology 215, 247–256 (2011). https://doi.org/10.1007/s00213-010-2132-0
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DOI: https://doi.org/10.1007/s00213-010-2132-0