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Effects of 18-methoxycoronaridine on ghrelin-induced increases in sucrose intake and accumbal dopamine overflow in female rats

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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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Authors and Affiliations

  1. Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY, 12208, USA

    Sarah E. McCallum, Olga D. Taraschenko, Ethan R. Hathaway, Melanie Y. Vincent & Stanley D. Glick

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  1. Sarah E. McCallum
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  2. Olga D. Taraschenko
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  3. Ethan R. Hathaway
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  4. Melanie Y. Vincent
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  5. Stanley D. Glick
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Corresponding author

Correspondence to Sarah E. McCallum.

Additional information

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

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