Nicotine reinforcement is reduced by cannabinoid CB1 receptor blockade in the ventral tegmental area.
Addiction Biology. 2012-07-11; 18(6): 930-936
DOI: 10.1111/j.1369-1600.2012.00476.x
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Cannabinoid type 1 (CB1) receptors control the motivational properties and
reinforcing effects of nicotine. Indeed, peripheral administration of a CB1
receptor antagonist dramatically decreases both nicotine taking and seeking.
However, the neural substrates through which the cannabinoid CB1 receptors
regulate the voluntary intake of nicotine remain to be elucidated. In the present
study, we sought to determine whether central injections of a CB1 receptor
antagonist delivered either into the ventral tegmental area (VTA) or the nucleus
accumbens (NAC) may alter nicotine intravenous self-administration (IVSA). Rats
were first trained to self-administer nicotine (30 μg/kg/0.1 ml). The effect of
central infusions of the CB1 antagonist AM 251 (0, 1 and 10 μg/0.5 μl/side) on
nicotine-taking behavior was then tested. Intra-VTA infusions of AM 251 dose
dependently reduced IVSA with a significant decrease for the dose
10 μg/0.5 μl/side. Moreover, operant responding for water was unaltered by
intra-VTA AM 251 at the same dose. Surprisingly, intra-NAC delivery of AM 251 did
not alter nicotine behavior at all. These data suggest that in rats chronically
exposed to nicotine IVSA, the cannabinoid CB1 receptors located in the VTA rather
than in the NAC specifically control nicotine reinforcement and, subsequently,
nicotine-taking behavior.
© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.
DOI: 10.1111/j.1369-1600.2012.00476.x
PMID: 22784230 [Indexed for MEDLINE]