Kappa-opioid receptor modulation of nicotine-induced behaviour

The ability of kappa -opioid receptor ligands to modulate dependence-relate d behavioural effects of drugs like morphine and cocaine is well documented . The present study examined the effects of kappa -opioid agonists on nicot ine-induced locomotor stimulation in rats chronically pre-exposed to nicoti ne (0.4 mg/kg/day). U50,488 [0.5-3 mg/kg subcutaneously (s.c.)], U69,593 [0 .08-0.32 mg/kg intraperitoneally (i.p.)] and CI-977 (0.005-0.02 mg/kg s.c.) administered 30 min prior to nicotine (0.06, 0.2 and 0.4 mg/kg s.c.) dose- dependently antagonised its acute locomotor-activating effect, which was co mpletely prevented by the highest tested dose of each agonist. Baseline act ivity was unaffected by the largest doses of U50,488 and U69,593, but it wa s reduced by 0.01 and 0.02 mg/kg of CI-977. The selective kappa -opioid rec eptor antagonist nor-BNI [30 mug intracerebroventricularly (i.c.v.)] blocke d the effects of U69,593 on nicotine-induced behaviour, thus supporting the involvement of kappa -opioid receptors in this effect. in conclusion, the activation of kappa -opioid receptors clearly prevented nicotine-induced lo comotor stimulation. The effects of at least two of the kappa -opioid agoni sts were not due to a general motor suppression. It is suggested that the m echanism entails a depression of nicotine-induced increases in accumbal dop amine by these compounds. The results should encourage further research on the role of the kappa -opioid system in the behavioural and neurochemical e ffects of nicotine, including those related to nicotine dependence. (C) 200 0 Elsevier Science Ltd. All rights reserved.