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Full-Text Articles in Life Sciences

Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker Aug 2008

Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker

Biomedical Sciences Faculty Research and Publications

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 cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the …


Contribution Of Cystine-Glutamate Antiporters To The Psychotomimetic Effects Of Phencyclidine, David A. Baker, Aric Madayag, Lars V. Kristiansen, James H. Meador-Woodruff, Vahram Haroutunian, Ilangovan Raju Jun 2008

Contribution Of Cystine-Glutamate Antiporters To The Psychotomimetic Effects Of Phencyclidine, David A. Baker, Aric Madayag, Lars V. Kristiansen, James H. Meador-Woodruff, Vahram Haroutunian, Ilangovan Raju

Biological Sciences Faculty Research and Publications

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect …