Role of the cannabinoid system in the effects induced
by nicotine on anxiety-like behaviour in mice

Balerio GN, Aso E, Maldonado R.
Laboratori de Neurofarmacologia,
Facultat de Ciencies de la Salut i de la Vida,
Universitat Pompeu Fabra,
C/ Doctor Aiguader 80, 08003, Barcelona, Spain,
Psychopharmacology (Berl). 2006 Jan 14;:1-10


RATIONALE: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. OBJECTIVES: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. METHODS: Animals were only exposed once to nicotine. The acute administration of low (0.05) or high (0.8 mg/kg, s.c.) doses of nicotine produced opposite effects in the elevated plus-maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, i.p.), and the cannabinoid agonist, Delta9-tetrahydrocannabinol (Delta9-THC, 0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. RESULTS: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, Delta9-THC failed to modify nicotine anxiolytic-like responses but attenuated its anxiogenic-like effects. In addition, the association of non-effective doses of Delta9-THC and nicotine produced clear anxiolytic-like responses. CONCLUSIONS: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.
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