The present study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knock-out mice lacking CB2r (CB2KO) and in wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/Kg). Gene expression analyses of tyrosine hydroxylase (TH), α3- and α4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate if CB2r co-localized with α3- and α4-nAChRs in the nucleus accumbens (NAcc) and VTA were performed. Mecamylamine-precipitated withdrawal syndrome after chronic nicotine exposure was evaluated in CB2KO mice and in WT mice treated with AM630 (1 and 3 mg/Kg). CB2KO mice did not show nicotine-induced place conditioning and self-administered significantly less nicotine. In addition, AM630 was able to block (3 mg/Kg) nicotine-induced CPP and reduce (1 and 3 mg/Kg) nicotine self-administration. Under baseline conditions, TH, α3- and α4-nAChRs mRNA levels in the VTA of CB2KO mice were significantly lower compared with WT mice. Confocal microscopy images revealed that CB2r co-localized with α3- and α4-nAChRs. Somatic signs of nicotine withdrawal (rearings, groomings, scratches, teeth chattering and body tremors) increased significantly in WT but were absent in CB2KO mice. Interestingly, the administration of AM630 blocked the nicotine withdrawal syndrome and failed to alter basal behavior in saline-treated WT mice. These results suggest that CB2r play a relevant role in the reinforcing and motivational effects of nicotine. Pharmacological manipulation of this receptor deserves further consideration as a potential new valuable target for the treatment of nicotine dependence.Neuropsychopharmacology accepted article preview online, 2 July 2013. doi:10.1038/npp.2013.157.

PMID:

 

23817165

 

[PubMed – as supplied by publisher]