title: 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, (2.5 mg/kg, subcutaneously), four times daily for 7 days. In order to precipitate nicotine withdrawal, mice were given one injection of mecamylamine (3 mg/kg, intraperitoneally) 1 h after the last nicotine injection on the test day (day 8). Behavioral observations were made for a period of 30 min 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.
authors.affiliation: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, 147002, Punjab, India. gurjeetthakur@gmail.com
authors.forename: Thakur Gurjeet
authors.initials: TG
authors.lastname: Singh
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Rehni
authors.forename: Sandeep
authors.initials: S
authors.lastname: Arora
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008464:Mecamylamine / Q000494:pharmacology*; D051379:Mice; D009538:Nicotine / Q000009:adverse effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000523:psychology
chemical_list: D007211:Indoles; D011758:Pyrroles; C085989:Ro 32-0432; D008464:Mecamylamine; D009538:Nicotine; D054774:G-Protein-Coupled Receptor Kinase 5