2006 年 6 巻 2 号 p. 43-50
The dopaminergic system plays an important role in emotional and rewarding properties, which may be a fundamental brain mechanism of mental functions such as emotion motivation and kansei. Cannabinoid compounds such as Δ9-tetrahydrocannabinol (Δ9-THC), a major active constituent of marijuana (Cannabis sativa), are responsible for central nervous system (CNS) effects. The CNS responses to cannabinoid compounds are mediated exclusively by CB1 cannabinoid receptors. To reveal the function of those receptors in dopamine release in projection areas of the mesolimbic and mesocortical dopaminergic fibers, we performed an in vitro superfusion experiment using synaptosomes from the nucleus accumbens, striatum or frontal cortex in rats. A high [K+] -induced release of dopamine was increased by CB 1 agonists, an effect that was blocked by pretreatment with a CB1 receptor antagonist SR141716A. This antagonist pretreatment also suppressed the high [K+] -induced release of dopamine. These results indicate that the CB1 receptor agonist increases the dopamine release from the depolarized synaptosomes through interaction with CB1 receptors. Furthermore, the results suggest the involvement of an endogenous cannabinoid system in the regulation of dopamine release from synaptic terminals. A neuronal modulation such as the depolarization-induced suppression of inhibition may act as one of the mechanisms underlying the cannabinoid effects on dopamine release.
