QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.058412v1 308/2/667    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leite-Morris, K. A. Articles by Kaplan, G. B. Search for Related Content PubMed PubMed Citation Articles by Leite-Morris, K. A. Articles by Kaplan, G. B.

NEUROPHARMACOLOGY

GABA_B Receptor Activation in the Ventral Tegmental Area Inhibits the Acquisition and Expression of Opiate-Induced Motor Sensitization

Center for Alcohol and Addiction Studies (K.A.L.-M., G.B.K.), Departments of Psychiatry and Human Behavior and Molecular Pharmacology, Physiology, and Biotechnology (E.Y.F., M.H.S., G.B.K), Brown Medical School, Providence, Rhode Island; and Research (K.A.L.-M.) and Mental Health (G.B.K.) Services, Veterans Affairs Medical Center, Providence, Rhode Island

Opiate-induced motor sensitization refers to the progressive and enduring motor response that develops after intermittent drug administration, and results from neuroadaptive changes in ventral tegmental area (VTA) and nucleus accumbens (NAc) neurons. Repeated activation of µ-opioid receptors localized on -aminobutyric acid (GABA) neurons in the VTA enhances dopaminergic cell activity and stimulates dopamine release in the nucleus accumbens. We hypothesize that GABA_B receptor agonist treatment in the VTA blocks morphine-induced motor stimulation, motor sensitization, and accumbal Fos immunoreactivity by inhibiting the activation of dopaminergic neurons. First, C57BL/6 mice were coadministered a single subcutaneous injection of morphine with intra-VTA baclofen, a GABA_B receptor agonist. Baclofen produced a dose-dependent inhibition of opiate-induced motor stimulation that was attenuated by 2-hydroxysaclofen, a GABA_B receptor antagonist. Next, morphine was administered on days 1, 3, 5, and 9 and mice demonstrated sensitization to its motor stimulant effects and concomitant induction of Fos immunoreactivity in the NAc shell (NAcS) but not NAc core. Intra-VTA baclofen administered during morphine pretreatment blocked the acquisition of morphine-induced motor sensitization and Fos activation in the NAcS. Intra-VTA baclofen administered only on day 9 blocked the expression of morphine-induced motor sensitization and Fos activation in the NAcS. A linear relationship was found between morphine-induced motor activity and accumbal Fos in single- and repeated-dose treatment groups. In conclusion, GABA_B receptor stimulation in the VTA blocked opiate-induced motor stimulation and motor sensitization by inhibiting the activation of NAcS neurons. GABA_B receptor agonists may be useful pharmacological treatments in altering the behavioral effects of opiates.

Address correspondence to: Drs. Kimberly Leite-Morris, Veterans Affairs Medical Center, Research Service (151), 830 Chalkstone Ave., Providence, RI 02908. E-mail: kimberly_leite-morris{at}brown.edu

This article has been cited by other articles:

				F. W. Hopf, M. Martin, B. T. Chen, M. S. Bowers, M. M. Mohamedi, and A. Bonci Withdrawal From Intermittent Ethanol Exposure Increases Probability of Burst Firing in VTA Neurons In Vitro J Neurophysiol, October 1, 2007; 98(4): 2297 - 2310. [Abstract] [Full Text] [PDF]