Bambang Subakti Zulkarnain and Junaidi Khotib, NIDN. 0022107001 (2008) Pivotel role reelin signaling pathway in the development of tolerance to morphine-induced antinociception. Indonesian Journal of Pharmacy, 19 (3). pp. 157-164. ISSN 2338-9486

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Abstract

The huge endogenous macromolecule protein responsible for controlling migration and dendritic growth of developing neurons, reelin, has recently been proposed that its signaling pathway modulates synaptic plasticity in the adult rodent brain. This study was carried out to investigate the pivotal role of the reelin signaling pathway in the development of tolerance to morphine-induced antinociception. There was evidence that repeated intracerebroventricular administration of reeling monoclonal antibody, the competitive inhibitor to reelin - apolipoprotein receptor E2 recombinant, and disabledl (Dabl) protein inhibitor - MG132, resulted in the inhibition to the development of antinociception tolerance to morphine administration. Furthermore, chronic in vivo administration with morphine caused significance increase of the immunoreactivity (IR) for phosphorylatedDabl in the thalamus. These data suggested that persistent activation of reelin signaling pathway due to chronic administration of morphine may be responsible for the development of tolerance to morphine-induced antinociception.

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