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The stimulating effects of ethanol on ventral tegmental area dopamine neurons projecting to the ventral pallidum and medial prefrontal cortex in female Wistar rats: regional difference and involvement of serotonin-3 receptors

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Abstract

Rationale

The ventral tegmental area (VTA) mediates the local stimulating effects of ethanol (EtOH) in a region-dependent manner, with EtOH administration in the posterior but not anterior VTA stimulating the mesolimbic system. The serotonin-3 (5-HT3) receptor has been involved in the effects of EtOH on the mesolimbic system.

Objectives

The current study tested the hypothesis that EtOH would stimulate mesopallidal and mesocortical dopamine neurons in the posterior but not anterior VTA and that the stimulating effects of EtOH in the VTA would involve activation of local 5-HT3 receptors.

Methods

Wistar female rats were surgically implanted with two cannulae, one in one sub-region of the VTA for microinjection and the other in the ventral pallidum (VP) or medial prefrontal cortex (mPFC) for microdialysis. Artificial cerebrospinal fluid or EtOH (200 mg%; 44 mM) was microinjected in the anterior or posterior VTA, and extracellular dopamine was measured in the VP or mPFC with microdialysis-HPLC.

Results

EtOH injections in the posterior but not anterior VTA significantly increased extracellular dopamine levels in the VP and mPFC. Co-injections of the 5-HT3 receptor antagonist ICS-205,930 with EtOH in the posterior VTA significantly reduced the effects of EtOH on extracellular dopamine levels in the VP and mPFC.

Conclusions

The results indicate that posterior VTA dopamine neurons projecting to the VP and mPFC are stimulated by local administration of EtOH and that the local stimulating effects of EtOH are mediated, at least in part, by 5-HT3 receptors.

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Acknowledgments

This study was supported by research grants AA07462, AA 10717, AA 10721, and AA 12262. We thank Amanda Moran and Brandon Dewell for their technical help.

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Authors and Affiliations

  1. Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN, 46202-4887, USA

    Zheng-Ming Ding, Scott M. Oster, Sarah R. Hall, Eric A. Engleman, Sheketha R. Hauser, William J. McBride & Zachary A. Rodd

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  1. Zheng-Ming Ding
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  2. Scott M. Oster
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  3. Sarah R. Hall
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Correspondence to Zheng-Ming Ding.

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Ding, ZM., Oster, S.M., Hall, S.R. et al. The stimulating effects of ethanol on ventral tegmental area dopamine neurons projecting to the ventral pallidum and medial prefrontal cortex in female Wistar rats: regional difference and involvement of serotonin-3 receptors. Psychopharmacology 216, 245–255 (2011). https://doi.org/10.1007/s00213-011-2208-5

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