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Altered sucrose self-administration following injection of melanocortin receptor agonists and antagonists into the ventral tegmental area

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Abstract

Rationale and objectives

Alpha-melanocyte stimulating hormone (αMSH) and agouti-related protein (AgRP) are antagonistic neuropeptides that play an important role in the control of feeding and body weight through their central actions on the melanocortin-3 and melanocortin-4 receptors. Increasing evidence indicates that αMSH and AgRP can interact with the mesolimbic dopamine system to regulate feeding as well as other behaviors. For example, we have shown previously that injection of melanocortin receptor agonists and antagonists into the ventral tegmental area (VTA) alters both normal home-cage feeding and the intake of sucrose solutions, but it remains unknown whether αMSH and AgRP can also act in the VTA to affect reward-related feeding.

Methods

We tested whether injection of the melanocortin receptor agonist, MTII, or the melanocortin receptor antagonist, SHU9119, directly into the VTA affected operant responding maintained by sucrose pellets in self-administration assays.

Results

Injection of MTII into the VTA decreased operant responding maintained by sucrose pellets on both fixed ratio and progressive ratio schedules of reinforcement, whereas SHU9119 increased operant responding under fixed ratio, but not progressive ratio schedules. MTII also increased and SHU9119 decreased 24-h home-cage food intake.

Conclusions

This study demonstrates that αMSH and AgRP act in the VTA to affect sucrose self-administration. Thus, it adds critical information to the growing literature showing that in addition to their well-characterized role in controlling “need-based” feeding, αMSH and AgRP can also act on the mesolimbic dopamine system to control reward-related behavior.

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Acknowledgements

Funding for these studies was provided by the Department of Biology and the Brains and Behavior Program at Georgia State University. We would like to thank Melissa Lange, Rapheal Williams, and Bonnie Williams for help and advice with performing the self-administration studies.

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Authors and Affiliations

  1. Department of Biology, Georgia State University, Atlanta, GA, 30303, USA

    Laranci Shanmugarajah, Anna I. Dunigan, Kyle J. Frantz & Aaron G. Roseberry

  2. Neuroscience Institute, Georgia State University, Atlanta, GA, 30303, USA

    Kyle J. Frantz & Aaron G. Roseberry

  3. Center for Obesity Reversal, State University, Atlanta, GA, 30303, USA

    Aaron G. Roseberry

Authors
  1. Laranci Shanmugarajah
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  2. Anna I. Dunigan
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  3. Kyle J. Frantz
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  4. Aaron G. Roseberry
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Correspondence to Aaron G. Roseberry.

Ethics declarations

All protocols and procedures were approved by the Institutional Animal Care and Use Committee at Georgia State University and conformed to the NIH Guide for the Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflict of interest.

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Shanmugarajah, L., Dunigan, A.I., Frantz, K.J. et al. Altered sucrose self-administration following injection of melanocortin receptor agonists and antagonists into the ventral tegmental area. Psychopharmacology 234, 1683–1692 (2017). https://doi.org/10.1007/s00213-017-4570-4

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  • DOI: https://doi.org/10.1007/s00213-017-4570-4

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