Archival ReportThe Role of Cystine-Glutamate Exchange in Nicotine Dependence in Rats and Humans
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Animals and Surgery
All procedures were conducted in accordance with the guidelines from the National Institutes of Health (NIH) and the Association for the Assessment and Accreditation of Laboratory Animal Care and were approved by the institute's Animal Use and Care Committee. Male Wistar rats weighing 250 g to 350 g were assigned to one of four groups: nicotine self-administration (N-SA; n = 10), saline (SAL; n = 10), nicotine osmotic minipump 1.3 mg/kg/day base (N-P1.3; n = 9), or nicotine osmotic minipump
Nicotine Self-Administration and Somatic Signs of Withdrawal
Rats self-administering nicotine for 21 days received an average dose of .95 ± .01 mg/kg per day nicotine base (Figure 1A). The relatively high rates of responding on the first day resulted from initial food training prior to nicotine self-administration, and in both groups stable baseline responding was achieved within the first 5 days of training. A two-way ANOVA revealed significant main effects of nicotine exposure [F(1,17) = 63.49, p < .001] and day [F(20,340) = 20.66, p < .001] but no
Discussion
Rats that self-administered nicotine intravenously showed a marked decrease in xCT in the nucleus accumbens and the VTA and GLT-1 expression in the nucleus accumbens relative to saline control animals. As well, xCT levels after nicotine self-administration were lower than in animals administered nicotine passively via continuous subcutaneous osmotic minipump delivery. These findings indicate that phasic administration of nicotine, rather than continuous release via minipumps, is necessary to
References (23)
Cerebral cystine uptake: A tale of two transporters
Trends Pharmacol Sci
(2002)- et al.
Glutamatergic substrates of drug addiction and alcoholism
Biochem Pharmacol
(2008) - et al.
A comparison of multiple injections versus continuous infusion of nicotine for producing up-regulation of neuronal [3H]-epibatidine binding sites
Neuropharmacology
(1997) Glutamate uptake
Prog Neurobiol
(2001)Exchange of cystine and glutamate across plasma membrane of human fibroblasts
J Biol Chem
(1986)- et al.
Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress
Neuron
(1989) - et al.
N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking
Biol Psychiatry
(2008) - et al.
Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse
Nat Neurosci
(2003) - et al.
Repeated N-acetylcysteine administration alters plasticity-dependent effects of cocaine
J Neurosci
(2007) - et al.
Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior
J Neurosci
(2003)
N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking
Biol Psychiatry
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LAK and SL contributed equally to this article.