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Effects of l ‐Cysteine on Reinstatement of Ethanol‐Seeking Behavior and on Reinstatement‐Elicited Extracellular Signal–Regulated Kinase Phosphorylation in the Rat Nucleus Accumbens Shell
Author(s) -
Peana Alessandra T.,
Giugliano Valentina,
Rosas Michela,
Sabariego Marta,
Acquas Elio
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01877.x
Subject(s) - nucleus accumbens , phosphorylation , extracellular , microbiology and biotechnology , ethanol , chemistry , kinase , cysteine , biochemistry , biology , receptor , enzyme
Background Alcoholism is a neuroadaptive disorder, and the understanding of the mechanisms of the high rates of relapse, which characterize it, represents one of the most demanding challenges in alcoholism and addiction research. The extracellular signal–regulated kinase ( ERK ) is an intracellular kinase, critical for neuroplasticity in the adult brain that is suggested to play a fundamental role in the molecular mechanisms underlying drug addiction and relapse. We previously observed that a nonessential amino acid, l ‐cysteine, significantly decreases oral ethanol ( E t OH ) self‐administration, reinstatement of E t OH ‐drinking behavior, and E t OH self‐administration break point. Methods Here, we tested whether l ‐cysteine can affect the ability of E t OH priming to induce reinstatement of E t OH ‐seeking behavior. In addition, we determined the ability of E t OH priming to induce ERK phosphorylation as well as the ability of l ‐cysteine to affect reinstatement‐elicited ERK activation. To these purposes, Wistar rats were trained to nose‐poke for a 10% v/v E t OH solution. After stable drug‐taking behavior was obtained, nose‐poking for E t OH was extinguished, and reinstatement of drug seeking, as well as reinstatement‐elicited pERK , was determined after an oral, noncontingent, priming of E t OH (0.08 g/kg). Rats were pretreated with either saline or l ‐cysteine (80 to 120 mg/kg) 30 minutes before testing for reinstatement. Results The findings of this study confirm that the noncontingent delivery of a nonpharmacologically active dose of E t OH to rats, whose previous self‐administration behavior had been extinguished, results in significant reinstatement into E t OH ‐seeking behavior. In addition, the results indicate that reinstatement selectively activates ERK phosphorylation in the shell of the nucleus accumbens ( A cb) and that pretreatment with l ‐cysteine reduces either reinstatement of E t OH seeking and reinstatement‐elicited pERK in the A cb S h. Conclusions Altogether, these results indicate that l ‐cysteine could be an effective pharmacological agent for the prevention of behavioral and molecular correlates of E t OH ‐primed reinstatement of E t OH seeking and that the shell of the A cb represents a critical neural substrate for priming‐elicited reinstatement mechanisms involving ERK phosphorylation.