Ro 32-0432 attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice

Abstract

G protein-coupled receptor kinase 5 is noted to mediate a number of signal transduction cascades involved in the causation of nicotine withdrawal syndrome. Therefore, the present study investigated the effect of Ro 32-0432, a G protein-coupled receptor kinase 5 inhibitor, on propagation of nicotine dependence and resultant withdrawal signs in subchronic nicotine mouse model. Our experimental protocol consisted of administration of nicotine, (2.5mg/kg, subcutaneously), four times daily for 7days. In order to precipitate nicotine withdrawal, mice were given one injection of mecamylamine (3mg/kg, intraperitoneally) 1h after the last nicotine injection on the test day (day8). Behavioral observations were made for a period of 30min immediately after mecamylamine treatment. Withdrawal syndrome was quantitated in terms of a composite withdrawal severity score, jumping frequency, nicotine-induced hyperalgesia by tail flick method, and withdrawal syndrome-related anxiety was assessed by elevated plus maze test results. Ro 32-0432 dose dependently attenuated mecamylamine-induced nicotine withdrawal syndrome in mice. It is concluded that Ro 32-0432 attenuates the propagation of nicotine dependence and reduce withdrawal signs possibly by G protein-coupled receptor kinase 5 activation-linked mechanisms.