title: 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.
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 whether L-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 of L-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 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 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 with L-cysteine reduces either reinstatement of EtOH seeking and reinstatement-elicited pERK in the AcbSh.
  
  
  CONCLUSIONS
  Altogether, these results indicate that L-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.
authors: Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. apeana@uniss.it
authors: Alessandra T
authors: AT
authors: Peana
authors: Valentina
authors: V
authors: Giugliano
authors: Michela
authors: M
authors: Rosas
authors: Marta
authors: M
authors: Sabariego
authors: Elio
authors: E
authors: Acquas
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000201:enzymology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003545:Cysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000008:administration & dosage*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D003545:Cysteine