Endocannabinoid system modulates relapse to methamphetamine seeking: Possible mediation by the arachidonic acid cascade

Kusnandar Anggadiredja, Masanori Nakamichi, Takato Hiranita, Hiroyuki Tanaka, Yukihiro Shoyama, Shigenori Watanabe, Tsuneyuki Yamamoto

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)


We clarified the modulating action of the endocannabinoid system, and its possible mediation by the arachidonic acid cascade, on the reinstatement of methamphetamine (METH)-seeking behavior, using the intravenous self-administration paradigm in rats. Following 12 days of self-administration of METH, the replacement of METH with saline resulted in a gradual decrease in lever press responses (extinction). Under extinction conditions, METH-priming or re-exposure to cues previously paired with METH infusion markedly increased the responses (reinstatement of drug-seeking). The cannabinoid CBI receptor antagonist, SR14171 6A, blocked this behavior. Although the cannabinoid agonist, Δ8-tetrahydrocannabinol (THC), had no effects by itself, coadministration of the agonist and METH at small doses reinstated the drug-seeking behavior. THC attenuated the effects of the reinstatement-inducing dose of METH, but enhanced the effect of cues. Either given repeatedly during the extinction or singly, 24 h before the first METH-priming or cues challenge, THC suppressed the reinstatement. In another set of experiments, we found that diclofenac, a cyclooxygenase inhibitor, also attenuated the reinstatement induced by exposure to cues or drug-priming. These results suggest that the endocannabinoid system, through possible mediation by the arachidonic acid cascade, serves as a modulator of the reinstating effects of METH-priming and cues. Extending the current view on the treatment of drug dependence, these results indicate that endocannabinoid-activating substances as well as cyclooxygenase inhibitors may be promising as antirelapse agents.

Original languageEnglish
Pages (from-to)1470-1478
Number of pages9
Issue number8
Publication statusPublished - Aug 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health


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