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Rewiring Cocaine Addiction: N‐Acetylcysteine Reverses Impaired Plasticity After Chronic Cocaine
Author(s) -
Moussawi Khaled,
Kalivas Peter W.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.905.9
Subject(s) - nucleus accumbens , long term potentiation , metabotropic glutamate receptor , neuroscience , pharmacology , glutamate receptor , addiction , nmda receptor , antagonist , psychology , medicine , dopamine , receptor
Neuroplasticity in the cortico‐striatal circuits contributes to the increased vulnerability to relapse and compulsive drug seeking in cocaine addiction. The details and mechanisms of these neuroadaptations are not fully elucidated. In this study, we test the ability of prefrontal‐accumbal synapses to express long term potentiation (LTP) or long term depression (LTD) after chronic cocaine. Rats were trained to self‐administer cocaine for 10 days, followed by 3 weeks of extinction, and field potentials recorded in the nucleus accumbens after prefrontal cortex stimulation, in vivo, under urethane anesthesia. Chronic cocaine impaired both LTP and LTD in rats treated with cocaine as compared to yoked saline or naïve rats. Systemic injection of N‐acetylcysteine (NAC), shown previously to block reinstatement, restored both LTP and LTD. Group II metabotropic glutamate receptor (mGluR) antagonist LY341495 selectively inhibited the ability of NAC to restore LTP, while the mGluR5 antagonist (MPEP) selectively inhibited the ability of NAC to restore LTD. Thus, chronic cocaine impairs accumbens plasticity, possibly by altering mGluR regulation of glutamate transmission. Support provided by DA015369.