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 journalArticle

97 Citations (Scopus)

Abstract

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
JournalNeuropsychopharmacology
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 1 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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    Anggadiredja, K., Nakamichi, M., Hiranita, T., Tanaka, H., Shoyama, Y., Watanabe, S., & Yamamoto, T. (2004). Endocannabinoid system modulates relapse to methamphetamine seeking: Possible mediation by the arachidonic acid cascade. Neuropsychopharmacology, 29(8), 1470-1478. https://doi.org/10.1038/sj.npp.1300454