Modulation of CREB expression and phosphorylation in the rat nucleus accumbens during nicotine exposure and withdrawal.

The nucleus accumbens region of the brain has been shown to play a role in reward and reinforcing mechanisms of drugs of abuse. To understand the molecular mechanisms of nicotine addiction, the present investigation examined the effects of acute and chronic nicotine treatment and its withdrawal on cAMP-responsive element binding (CREB) protein expression and phosphorylation (serine-133) in nucleus accumbens (NAc) structures of rats. it was found that acute treatment (1 and 18 hr of withdrawal) with nicotine had no effects on total creb and phosphorylated CREB (p-CREB) protein levels in shell or core structures of rat NAc. On the other hand, 18-hr withdrawal after chronic nicotine exposure produced significant reductions in the total CREB and p-CREB protein levels in the shell but not in core structures of nac. interestingly, nicotine withdrawal (1 hr) after chronic exposure maintained normal levels of total CREB and p-CREB protein levels in the shell and core structures of NAc. These results suggest the possibility that decreased CREB activity in the shell of NAc may be associated with abnormal reward mechanisms during nicotine withdrawal after chronic exposure.