An NMDA antagonist (LY 235959) attenuates abstinence-induced withdrawal of planarians following acute exposure to a cannabinoid agonist (WIN 55212-2).
The mechanisms that facilitate the development and expression of cannabinoid physical dependence in humans and other mammals are poorly understood. The present experiments used a planarian model to provide evidence that pharmacological antagonism of NMDA receptors significantly attenuates the development of cannabinoid physical dependence. Abstinence-induced withdrawal from the cannabinoid agonist WIN 55212-2 (10 microM) was manifested as a significant (P<0.05) decrease in the rate of planarian spontaneous locomotor velocity (pLMV) when WIN 55212-2 (10 microM)-exposed planarians were placed into drug-free water. No change in pLMV occurred when WIN 55212-2 (10 microM)-exposed planarians were placed into water containing WIN 55212-2 (10 microM). WIN 55212-2 (10 microM)-exposed planarians placed into water containing LY 235959 (1 or 10 microM) did not display withdrawal (no significant difference, P>0.05, in pLMV). In addition, withdrawal was not observed (no significant difference, P>0.05, in pLMV) in planarians that were co-exposed to a solution containing WIN 55212-2 (10 microM) and LY 235959 (10 microM). The present results reveal that NMDA receptor activation mediates the development of cannabinoid physical dependence and the expression of cannabinoid withdrawal in planarians.
Rawls
Scott M
SM
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Temple University School of Medicine, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Gomez
Teresa
T
Raffa
Robert B
RB
D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D002186:Cannabinoids / Q000819:agonists* / Q000633:toxicity; D007546:Isoquinolines / Q000494:pharmacology*; D002189:Marijuana Abuse / Q000188:drug therapy / Q000503:physiopathology; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010932:Planarians / Q000187:drug effects* / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control
D048588:Benzoxazines; D002186:Cannabinoids; D007546:Isoquinolines; D009025:Morpholines; D009281:Naphthalenes; D016194:Receptors, N-Methyl-D-Aspartate; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C088643:LY 235959