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Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats

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Abstract

Rationale

Increased excitatory output from the medial prefrontal cortex (mPFC) is thought to play a key role in the development of sensitization to cocaine. Gamma-aminobutyric acid (GABA) inhibits this excitatory output.

Objectives

The present studies were designed to determine the effects of intra-mPFC injections of the GABAB agonist baclofen on cocaine-induced motor activity and on the development of sensitization to cocaine.

Methods

Rats received bilateral cannula implants above the ventral mPFC. Initial studies examined the dose–response effects of injection of baclofen (0.05–0.5 nmol/side) into the mPFC on the acute motor-stimulant response to cocaine (15 mg/kg, i.p.). Additional studies determined whether coadministration of intra-mPFC baclofen (0.5 nmol/side) and systemic cocaine (15 mg/kg, i.p.) could alter the initiation and/or expression of cocaine-induced behavioral sensitization.

Results

Intra-mPFC baclofen dose-dependently blocked cocaine-induced motor activity. In sensitization studies, intra-mPFC baclofen was able to prevent the initiation, but not the expression of cocaine-induced sensitization.

Conclusions

The data suggest that the ability of GABA to modulate excitatory output from the mPFC may be attenuated in animals sensitized to cocaine.

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Acknowledgements

This research was supported by USPHS grants DA13470 and DA15965 (J.D.S.). The authors would like to thank Tim Walsh and Lori Ellis for technical assistance.

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Author notes

  1. Chad E. Beyer

    Present address: Depression and Anxiety Research, Discovery Neuroscience, Wyeth Ayerst, CN 8000, Princeton, NJ, 08543, USA

Authors and Affiliations

  1. Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue/Room 115 Crowe, Memphis, TN, 38163, USA

    Jeffery D. Steketee & Chad E. Beyer

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  1. Jeffery D. Steketee
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Correspondence to Jeffery D. Steketee.

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Steketee, J.D., Beyer, C.E. Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats. Psychopharmacology 180, 352–358 (2005). https://doi.org/10.1007/s00213-005-2149-y

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  • DOI: https://doi.org/10.1007/s00213-005-2149-y

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