Repeated Cocaine Administration Impairs Group Ii Metabotropic Glutamate Receptor-mediated Long-term Depression in Rat Medial Prefrontal Cortex.
From: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Mar 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 11
- Pages: 2958-68
- Medium: Internet
- Language: English
- Citation (JAMA): Huang Chiung-Chun, Yang Ping-Chun, Lin Hsiao-Ju, et al. Repeated Cocaine Administration Impairs Group Ii Metabotropic Glutamate Receptor-mediated Long-term Depression in Rat Medial Prefrontal Cortex.. J. Neurosci. Mar 2007;27:2958-68
Abstract
Drug-induced neuroadaptations within the medial prefrontal cortex (mPFC) are thought to underlie the development of cocaine sensitization. Here, we report that repeated cocaine administration in vivo impaired the long-term depression (LTD) induced by bath application of group II metabotropic glutamate receptor (mGluR) agonists DCG-IV [2S, 2’R, 3’R)-2-(2’, 3’-dicarboxycyclopropyl)glycine] or LY379268 [(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid] at excitatory synapses onto layer V pyramidal neurons of rat mPFC. In contrast, this impairment was not found in slices from rats treated with saline or a single dose of cocaine. Such effect of cocaine was selectively prevented when cocaine was coadministered with the selective D1-like receptor antagonist SCH23390 [(R)-(+)-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine]. In slices from control rats, a brief application of either protein kinase C (PKC) activator phorbol-12,13-dibutyrate or adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5-N-methyluronamide mimicked the effect of repeated cocaine treatment to impair the induction of LTD. Bilateral intra-mPFC infusion of PKC inhibitor bisindolylmaleimide I or adenosine A3 receptor antagonist MRS1220 (N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide) before cocaine injection prevented cocaine-induced impairment of LTD induction. Furthermore, endogenous adenosine tone is greater in slices from cocaine-treated rats than from the saline-treated controls. When the metabolism of cAMP to adenosine was blocked, the extent of LTD in slices from saline and cocaine-treated rats was similar. These results suggest that cocaine-induced impairment of group II mGluR-mediated LTD is caused, at least in part, by an increase in adenosine subsequent to the rise in cAMP after D1-like receptor activation, which leads to an adenosine A3 receptor-mediated upregulation of PKC activity and thereby triggers an inhibition of group II metabotropic glutamate receptor function.
Mesh Headings (Keywords): Animals, Cocaine, Long-Term Synaptic Depression, Male, Prefrontal Cortex, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate
Check for Full Text / PubMed Unique Identifier (PMID): 17360919
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