Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal.
OBJECTIVE
To study the changes in the expression and phosphorylation of cAMP response element binding protein (CREB) in the rat nucleus accumbens after chronic ethanol intake and its withdrawal.


METHODS
Ethanol was given in drinking water at the concentration of 6 % (v/v), for one month. Changes in the levels of CREB and phospho-CREB (p-CREB) protein in the nucleus accumbens were measured by immunohistochemistry methods.


RESULTS
Ethanol given to rats in drinking water decreased the level of p-CREB protein in the nucleus accumbens (-75 %) at the time of exposure to ethanol. The decrement of p-CREB protein in the nucleus accumbens remained at 24 h (-35 %) and 72 h (-28 %) of ethanol withdrawal, which recovered toward control level after 7 d of ethanol withdrawal. However, chronic ethanol, as well as ethanol withdrawal failed to produce any significant alteration in the level of CREB protein in the nucleus accumbens. Naloxone (alone) treatment of rats had no effect on the levels of CREB and p-CREB protein in the nucleus accumbens. However, when naloxone was administered concurrently with ethanol treatment, it antagonized the down-regulation of p-CREB protein in the nucleus accumbens (142 %) of rats exposed to ethanol.


CONCLUSIONS
A long-term intake of ethanol solution down-regulates the phosphorylation of CREB in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kind of the molecular mechanisms associated with ethanol dependence.
Li
Jing
J
Department of Pathology and Pathophysiology, Nanjing Medical University, Nanjing 210029, China. wlbianjs@163.com
Li
Yue-Hua
YH
Yuan
Xiao-Ru
XR
D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D009270:Naloxone; D000431:Ethanol