Jpn. J. Pharmacol. 84 (4), 229-236 (2000)
-Current Perspective-
Role of Cannabinoid Receptor in the Brain as It Relates to Drug Reward
Tsuneyuki Yamamoto1,* and Kohji Takada2
1Department of Pharmacology, Graduate school of Pharmaceutical
Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582, Japan
2Worldwide Scientific Affairs, Philip Morris K.K., Sanno Park
Tower 22F, 2-11-1 Nagata-cho, Chiyoda-ku, Tokyo 100-6190, Japan
*Corresponding author.ÊÊFAX:+81-92-642-6632
E-mail: yamamoto@yakuri.phar.kyushu-u.ac.jp
Philip Morris has not been involved in the preparation
of the manuscript either directly or indirectly and the authors opinions
may not represent those of Philip Morris.
Abstract: Understanding of cannabinoid (CB) actions has been
remarkably advanced during the last decade, due mainly to the identification
of the G-protein-coupled cannabinoid receptors, namely, CB1 receptors
that are predominantly found in the brain and CB2 receptors that are exclusively
found in peripheral tissues. Endogenous ligands for these receptors have
also been identified. Research to date suggests that the analgesic effect
of cannabinoids and the enhancement of opioid analgesia by cannabinoids
are both CB1 receptor-mediated via the activation of opioid receptors. The
involvement of the CB1 receptor in mediating reinforcing and physical dependence-producing
effects of opioids has also been suggested, with the former being considered
the result of interaction with the dopaminergic neurotransmission in the
midbrain dopamine system. However, the discriminative stimulus effects of
cannabinoids have been reported to be highly specific in that the effects
were not substituted by other classes of compounds including opioidergic
and dopaminergic agents nor were they antagonized by antagonists of various
neurotransmission systems, suggesting that the discriminative stimulus effects
only involve the cannabinoid system. Thus the cannabinoid actions appear
to be classifiable into at least two kinds: 1) those mediated directly through
cannabinoid receptors and 2) those mediated indirectly through other systems
such as opioidergic systems. Detailed research into these actions may help
to elucidate not only the mechanisms of action of exogenous cannabinoids
but also the role of endogenous cannabinoids, especially in the brain reward
system.
Keywords: Cannabinoid receptor, Drug reward system, Antinociceptive effect,
Discriminative stimulus property
Copyright© The Japanese Pharmacological Society 2000
[Back to TOC]