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Repeated cocaine treatment and withdrawal produces changes in brain function thought to be involved in relapse to drug use. Withdrawal from repeated cocaine reduced in vivo extracellular glutamate in the nucleus accumbens of rats by decreasing the exchange of extracellular cystine for intracellular glutamate. In vivo restoration of cystine/glutamate(More)
Basal extracellular glutamate sampled in vivo is present in micromolar concentrations in the extracellular space outside the synaptic cleft, and neither the origin nor the function of this glutamate is known. This report reveals that blockade of glutamate release from the cystine-glutamate antiporter produced a significant decrease (60%) in extrasynaptic(More)
Repeated cocaine produces enduring neuroadaptations in glutamate transmission in the nucleus accumbens that are thought to contribute to addiction. Group II metabotropic glutamate autoreceptors (mGluR2/3) regulate glutamate release, and this study investigates whether repeated cocaine injection produces long-lasting alterations in mGluR2/3 content,(More)
Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine-glutamate exchange via system xc-, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc-. First, we examined whether the(More)
The present study aimed to characterize a functional role for group I metabotropic glutamate receptors (mGluRs) in the nucleus accumbens and the capacity of repeated cocaine to elicit long-term changes in group I mGluR function. Reverse dialysis of the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) into the nucleus accumbens resulted in an increase(More)
Cocaine produces a persistent reduction in cystine-glutamate exchange via system x(c)- in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System x(c)- influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by(More)
The regulation of extracellular glutamate in the nucleus accumbens by group II metabotropic glutamate receptors (mGluR2/3) was examined in vivo. Stimulation of mGluR2/3 with 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or N-acetylaspartylglutamate reduced extracellular glutamate levels. Conversely, blockade of mGluR2/3 by LY143495 or(More)
Repeated administration of cocaine lowers the basal extracellular levels of glutamate in the nucleus accumbens as measured by microdialysis. The studies presented reveal that this long-term neuroadaptation elicited by repeated cocaine results from a decrease in the activity of cystine/glutamate exchange.
Addiction is a chronic relapsing disorder hypothesized to be produced by drug-induced plasticity that renders individuals vulnerable to craving-inducing stimuli such as re-exposure to the drug of abuse. Drug-induced plasticity that may result in the addiction phenotype includes increased excitatory signaling within corticostriatal pathways that correlates(More)