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Activation of brain prostanoid EP3 receptors via arachidonic acid cascade during behavioral suppression induced by Δ 8 ‐tetrahydrocannabinol
Author(s) -
Yamaguchi Taku,
Kubota Takashi,
Watanabe Shigenori,
Yamamoto Tsuneyuki
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02151.x
Subject(s) - cannabinoid , prostanoid , cannabinoid receptor , pharmacology , chemistry , prostaglandin e , receptor , endocrinology , receptor antagonist , medicine , antagonist , biochemistry
Abstract We have previously shown that behavioral changes induced by cannabinoid were due to an elevation of prostaglandin E 2 (PGE 2 ) via the arachidonic acid cascade in the brain. In the present study, we investigated the participation of the prostanoid EP3 receptor, the target of PGE 2 in the brain, in behavioral suppression induced by Δ 8 ‐tetrahydrocannabinol (Δ 8 ‐THC), an isomer of the naturally occurring Δ 9 ‐THC, using a one‐lever operant task in rats. Intraperitoneal administration of Δ 8 ‐THC inhibited the lever‐pressing behavior, which was significantly antagonized by both the selective cannabinoid CB1 receptor antagonist SR141716A and the cyclooxygenase inhibitor diclofenac. Furthermore, intracerebroventricular (i.c.v.) administration of PGE 2 significantly inhibited the lever‐pressing performance similar to Δ 8 ‐THC. Prostanoid EP3 receptor antisense‐oligodeoxynucleotide (AS‐ODN; twice a day for 3 days, i.c.v.) significantly decreased prostanoid EP3 receptor mRNA levels as determined by the RT‐PCR analysis in the cerebral cortex, hippocampus and midbrain. AS‐ODN also antagonized the PGE 2 ‐induced suppression of the lever pressing. In the same way, the suppression of lever‐pressing behavior by Δ 8 ‐THC was significantly improved by AS‐ODN. It is concluded that the suppression of lever‐pressing behavior by cannabinoid is due to activation of the prostanoid EP3 receptor through an elevation of PGE 2 in the brain.