@article {2338,
	title = {The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine.},
	journal = {Biol Psychiatry},
	volume = {71},
	number = {11},
	year = {2012},
	month = {2012 Jun 1},
	pages = {978-86},
	abstract = {BACKGROUND: Relapse to cocaine seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine seeking, and depotentiate PFC-NAcore synapses. Here, we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5).

METHODS: Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, before inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures.

RESULTS: NAC microinjection into the NAcore inhibited the reinstatement of cocaine seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in an mGluR2/3-dependent manner, while high doses of NAC increased amplitude in an mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine seeking by NAC was potentiated.

CONCLUSIONS: The effect of NAC on relapse to cocaine seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5.},
	keywords = {Acetylcysteine, Animals, Cocaine, Cystine, Drug-Seeking Behavior, Excitatory Postsynaptic Potentials, Free Radical Scavengers, Glutamic Acid, Male, Nucleus Accumbens, Patch-Clamp Techniques, Prefrontal Cortex, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Recurrence, Synaptic Transmission},
	issn = {1873-2402},
	doi = {10.1016/j.biopsych.2011.10.024},
	author = {Kupchik, Yonatan M and Moussawi, Khaled and Tang, Xing-Chun and Wang, Xiusong and Kalivas, Benjamin C and Kolokithas, Rosalia and Ogburn, Katelyn B and Kalivas, Peter W}
}
