Time-dependent change of ERK phosphorylation levels in the nucleus accumbens during withdrawals from repeated cocaine

Extracellular signal-regulated kinase (ERK) has been implicated in cocaine-induced behavioral sensitization. We sought to determine whether ERK activation in the nucleus accumbens (NAcc), the site mediating the expression of behavioral sensitization, shows time-dependent changes after cocaine withdrawals. The basal levels of ERK phosphorylation in the NAcc show no changes on withdrawal day 1, while they increase on day 7, then gradually lower down to reach the same level on day 21 in cocaine compared to saline pre-exposed rats. Either total ERK or both phosphorylated and total p38 protein levels are not different in any time-point measurements. These results suggest that such time-dependent ERK activation in the NAcc may contribute to neuronal plasticity leading to long-lasting behavioral changes such as drug craving.