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Role of GABAA receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats

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Abstract

Rationale

The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our data indicate that stress inhibits the dorsal raphe nucleus (DRN)-5-HT system via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor and, more recently, that morphine history sensitizes DRN-5-HT neurons to GABAergic inhibitory effects of stress.

Objectives

We tested the hypothesis that DRN GABAA receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP).

Methods

First, we tested if activation of GABAA receptors in the DRN would reinstate morphine CPP. Second, we tested if blockade of GABAA receptors in the DRN would attenuate swim stress-induced reinstatement of morphine CPP. CPP was induced by morphine (5 mg/kg) in a 4-day conditioning phase followed by a conditioning test. Upon acquiring conditioning criteria, subjects underwent 4 days of extinction training followed by an extinction test. Upon acquiring extinction criteria, animals underwent a reinstatement test. For the first experiment, the GABAA receptor agonist muscimol (50 ng) or vehicle was injected into the DRN prior to the reinstatement test. For the second experiment, the GABAA receptor antagonist bicuculline (75 ng) or vehicle was injected into the DRN prior to a forced swim stress, and then, animals were tested for reinstatement of CPP.

Results

Intraraphe injection of muscimol reinstated morphine CPP, while intraraphe injection of bicuculline attenuated swim stress-induced reinstatement.

Conclusions

These data provide evidence that GABAA receptor-mediated inhibition of the serotonergic DRN contributes to stress-induced reinstatement of morphine CPP.

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Acknowledgments

This research was supported by NIH R01 DA 20126 and NIH P30 DA 13429.

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All authors declare no conflict of interests and have no disclosures.

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Authors and Affiliations

  1. Center for Substance Abuse Research and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3500 N. Broad St., Philadelphia, PA, 19140, USA

    Chen Li, Daniel R. Staub & Lynn G. Kirby

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  1. Chen Li
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  2. Daniel R. Staub
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  3. Lynn G. Kirby
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Correspondence to Lynn G. Kirby.

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Li, C., Staub, D.R. & Kirby, L.G. Role of GABAA receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats. Psychopharmacology 230, 537–545 (2013). https://doi.org/10.1007/s00213-013-3182-x

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  • DOI: https://doi.org/10.1007/s00213-013-3182-x

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