Extracellular signal-regulated kinases (ERK1 and ERK2) may play an important role in the molecular mechanisms of opiates addiction. Recently, the role of hippocampus in the process of addiction has attracted an attention as addictive drugs like morphine may affect the normal function of this region leading to a formation of aberrant learning. Our previous results demonstrated that acute and prolonged morphine treatment leads to changes of ERK1 and ERK2 phosphorylation. However, the specifi c pattern of alterations of ERK1 and ERK2 phosphorylation (which is required for ERKs activity) in the hippocampus, during the development of morphine reward has not been studied yet. We discovered that fi rst morphine conditioning increased ERK1 and ERK2 phosphorylation in CPP paradigm, but after third morphine session during CPP, we observed the decrease of ERK1 and ERK2 phosphorylation. Moreover, an increase of pERK2/pERK1 ratio correlated linearly with the expression of place preference following morphine administration. The changes of phosphorylation were observed in mossy fi bers, the structure, which is involved in spatial learning and memory. In hippocampus, the observed changes of ERK phosphorylation favoring mainly ERK2 activity together with the putative role of ERK2 in learning and long-term memory suggest that morphine-induced interactions within ERK pathway participate in reward-controlled learning. Research supported by Ministry of Science and Education Grant N401 066 31/168.
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