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. (23rd July 2012)

• Record Type: Journal Article
• Authors: Peana, Alessandra T.; Giugliano, Valentina; Rosas, Michela; Sabariego, Marta; Acquas, Elio
• Is Part Of: Alcoholism. Volume 37(2013)Supplement 1
• Page Start: E329
• Page End: E337
• Publication Date: 2012-07-23
• Subjects: l‐Cysteine -- Ethanol‐Primed Reinstatement -- Ethanol‐Seeking Behavior -- Reinstatement‐Elicited ERK Activation -- Nucleus Accumbens Shell; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/j.1530-0277.2012.01877.x
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : 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 (EtOH) self‐administration, reinstatement of EtOH‐drinking behavior, and EtOH self‐administration break point. Methods: Here, we tested whetherl ‐cysteine can affect the ability of EtOH priming to induce reinstatement of EtOH‐seeking behavior. In addition, we determined the ability of EtOH priming to induce ERK phosphorylation as well as the ability ofl ‐cysteine to affect reinstatement‐elicited ERK activation. To these purposes, Wistar rats were trained to nose‐poke for a 10% v/v EtOH solution. After stable drug‐taking behavior was obtained, nose‐poking for EtOH was extinguished, and reinstatement of drug seeking, as well as reinstatement‐elicited pERK, was determined after an oral, noncontingent, priming of EtOH (0.08 g/kg). Rats were pretreated with either saline orl ‐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 EtOH to rats, whose previous self‐administration behavior had been extinguished, results in significant reinstatement into EtOH‐seeking behavior. In addition, the results indicate that reinstatement selectively activates ERK phosphorylation in the shell of the nucleus accumbens (Acb) and that pretreatment withl ‐cysteine reduces either reinstatement of EtOH seeking and reinstatement‐elicited pERK in the AcbSh. Conclusions: Altogether, these results indicate thatl ‐cysteine could be an effective pharmacological agent for the prevention of behavioral and molecular correlates of EtOH‐primed reinstatement of EtOH seeking and that the shell of the Acb represents a critical neural substrate for priming‐elicited reinstatement mechanisms involving ERK phosphorylation.