Alterations in ionotropic glutamate receptor subunits during binge cocaine self-administration and withdrawal in rats.
Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in glutamatergic function in brain regions associated with reinforcement. Previous studies have examined ionotropic glutamate receptor (iGluR) subunit protein level changes following acute and chronic experimenter-administered cocaine or after withdrawal periods from experimenter-administered cocaine. To evaluate whether alterations in expression of iGluRs are associated with cocaine reinforcement, protein levels were assessed after binge (8 h/day, 15 days; 24-h access, days 16-21) cocaine self-administration and following 2 weeks of abstinence from this binge. Western blotting was used to compare levels of iGluR protein expression (NR1-3B, GluR1-7, KA2) in the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) of rats. iGluR subunits were altered in a time-dependent manner in all brain regions studied; however, selective alterations in certain iGluR subtypes appeared to be associated with binge cocaine self-administration and withdrawal in a region-specific manner. In the SN and VTA, alterations in iGluR protein levels compared with controls occurred only following binge access, whereas in the striatum and PFC, iGluR alterations occurred with binge access and following withdrawal. In the NAc, GluR2/3 levels were increased following withdrawal compared with binge access, and were the only changes observed in this region. Because subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine.
Tang
Wenxue
W
Department of Pharmacology, Yerkes National Primate Research Center, Neuroscience Division, Emory University School of Medicine, Atlanta, Georgia 30329, USA.
Wesley
Michael
M
Freeman
Willard M
WM
Liang
Bill
B
Hemby
Scott E
SE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D021122:Protein Subunits; D017470:Receptors, Glutamate; D003042:Cocaine