Cannabinoid suppressed bicuculline-induced convulsion without respiratory depression in the brainstem-spinal cord preparation from newborn rats.
Previous studies have suggested that cannabinoid compounds are anticonvulsants and that these compounds depress respiratory activity. However, the anticonvulsant potential of cannabinoids and their depressive effect on respiration have not been evaluated simultaneously. In the present study, we used a brainstem-spinal cord preparation model to investigate changes in inspiratory activity and the anticonvulsant effects of a cannabinoid receptor agonist, WIN 55, 212-2, in bicuculline-induced convulsion. Application of 10 microM WIN 55, 212-2 caused no change in inspiratory activity (6.9+/- 0.89 bursts/min vs. 8.0+/- 1.3 bursts/min, not significant) and decreased bicuculline-induced seizure-like nerve activity (number of seizure-like activities in 10 min, 11+/- 7.4 bursts vs. 1.5+/- 1.6 bursts, P< 0.01; average duration of seizure-like activity, 8.9+/- 4.0 sec vs. 4.7+/- 2.1 sec, P> 0.01). Our results suggest that administration of an appropriate dose of cannabinoid receptor agonist WIN 55,212-2 has an anticonvulsant effect but does not cause respiratory depression.
Koda
Shusuke
S
Department of Anesthesiology and Intensive Care, Nippon Medical School, Tokyo, Japan. koda@nms.ac.jp
Takeda
Shinhiro
S
Onimaru
Hiroshi
H
Akada
Shinji
S
Sakamoto
Atsuhiro
A
D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines; D001640:Bicuculline / Q000494:pharmacology*; D001933:Brain Stem / Q000503:physiopathology*; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000503:physiopathology*
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003292:Convulsants; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D001640:Bicuculline