It is known that acute cocaine administration activates the extracellular signal-regulated kinase (ERK) pathway in the striatum, and results in transcription and translation of immediate early genes (IEGs). In the present study we investigated a possible involvement of ERK in the regulation of IEG expression in the amygdala, another brain structure known to be related to an addicted state. The patterns of cocaine-induced c-Fos, JunB and Zif268 protein expression were investigated, using an immunohistochemical approach, within distinct nuclei of the amygdala, either in the presence or absence of a selective inhibitor of the ERK pathway, SL327. Although these IEGs were similarly activated in the various nuclei of the amygdala after acute administration of cocaine, they showed different patterns after chronic injections. They also showed selective sensitivities to ERK inhibition. In particular, whereas c-Fos and JunB expressions were augmented following chronic cocaine treatment, as compared with acute treatment, Zif268 expression was decreased by this chronic treatment. Additionally, chronic blocking of ERK activation affected cocaine-induced c-Fos and JunB but not Zif268 expression. Thus, the differential involvement of ERK in chronic vs. acute regulation of IEGs may account for its specific role in addiction-related behavioral alterations, such as sensitization and tolerance.
