title: Group II metabotropic glutamate receptors in the striatum of non-human primates: dysregulation following chronic cocaine self-administration.
abstract: A growing body of evidence has demonstrated a role for group II metabotropic glutamate receptors (mGluRs) in the reinforcing effects of cocaine. These receptors are important given their location in limbic-related areas, and their ability to control the release of glutamate and other neurotransmitters. They are also potential targets for novel pharmacotherapies for cocaine addiction. The present study investigated the impact of chronic cocaine self-administration (9.0mg/kg/session for 100 sessions, 900 mg/kg total intake) on the densities of group II mGluRs, as assessed with in vitro receptor autoradiography, in the striatum of adult male rhesus monkeys. Binding of [(3)H]LY341495 to group II mGluRs in control animals was heterogeneous, with a medial to lateral gradient in binding density. Significant elevations in the density of group II mGluRs following chronic cocaine self-administration were measured in the dorsal, central and ventral portions of the caudate nucleus (P<0.05), compared to controls. No differences in receptor density were observed between the groups in either the putamen or nucleus accumbens. These data demonstrate that group II mGluRs in the dorsal striatum are more sensitive to the effects of chronic cocaine exposure than those in the ventral striatum. Cocaine-induced dysregulation of the glutamate system, and its consequent impact on plasticity and synaptic remodeling, will likely be an important consideration in the development of novel pharmacotherapies for cocaine addiction.
authors: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA. tbeverid@wfubmc.edu
authors: T J R
authors: TJ
authors: Beveridge
authors: H R
authors: HR
authors: Smith
authors: M A
authors: MA
authors: Nader
authors: L J
authors: LJ
authors: Porrino
mesh_terms: D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001345:Autoradiography; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods; D014316:Tritium / Q000493:pharmacokinetics; D014966:Xanthenes / Q000493:pharmacokinetics
chemical_list: D000596:Amino Acids; D000963:Antimetabolites; D002247:Carbon Isotopes; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D014316:Tritium; D003847:Deoxyglucose; D003042:Cocaine; C104722:glutamate receptor ionotropic, AMPA 2