title: Repeated exposure to cocaine alters the modulation of mesocorticolimbic glutamate transmission by medial prefrontal cortex Group II metabotropic glutamate receptors.
abstract: Repeated cocaine exposure enhances glutamatergic output from the medial prefrontal cortex to subcortical brain regions. Loss of inhibitory control of cortical pyramidal neurons may partly account for this augmented cortical glutamate output. Recent research indicated that repeated cocaine exposure reduced the ability of cortical Group II metabotropic glutamate receptors to modulate behavioral and neurochemical responses to cocaine. Thus, experiments described below examined whether repeated cocaine exposure alters metabotropic glutamate receptor regulation of mesocorticolimbic glutamatergic transmission using in vivo microdialysis. Infusion of the Group II metabotropic glutamate receptor antagonist LY341495 into the medial prefrontal cortex enhanced glutamate release in this region, the nucleus accumbens and the ventral tegmental area in sensitized animals, compared to controls, following short-term withdrawal but not after long-term withdrawal. Additional studies demonstrated that vesicular (K(+)-evoked) and non-vesicular (cystine-evoked) glutamate release in the medial prefrontal cortex was enhanced in sensitized animals, compared to controls, that resulted in part from a reduction in Group II metabotropic glutamate receptor modulation of these pools of glutamate. In summary, these findings indicate that the expression of sensitization to cocaine is correlated with an altered modulation of mesocorticolimbic glutamatergic transmission via reduction of Group II metabotropic glutamate receptor function.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Xie
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Steketee
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003553:Cystine / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid; D003553:Cystine; D003042:Cocaine