The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats.
Previous studies in animals and humans have shown that, in some cases at least, anti-epileptic drugs can reduce the severity of tinnitus. Given that cannabinoid receptor agonists have been shown to exert anti-epileptic effects in some circumstances, we investigated whether two synthetic CB(1)/CB(2) receptor agonists, WIN55,212-2, and CP55,940, could inhibit the behavioural manifestations of salicylate-induced tinnitus in rats in a conditioned suppression task. We found that neither WIN55,212-2 (3.0 mg/kg s.c) nor CP55,940 (0.1 or 0.3 mg/kg s.c), significantly reduced conditioned behaviour associated with tinnitus. However, both 3 mg/kg WIN55,212-2 and 0.3 mg/kg CP55,940 did significantly increase tinnitus-related behaviour compared to the vehicle control groups. These results suggest that cannabinoid receptor agonists may not be useful in the treatment of salicylate-induced tinnitus and that at certain doses, they could actually exacerbate the condition.
Zheng
Yiwen
Y
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, PO Box 913, Dunedin, New Zealand. yiwen.zheng@stonebow.otago.ac.nz
Stiles
Lucy
L
Hamilton
Emma
E
Smith
Paul F
PF
Darlington
Cynthia L
CL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology* / Q000633:toxicity; D003216:Conditioning, Operant / Q000187:drug effects*; D003511:Cyclohexanols / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009025:Morpholines / Q000494:pharmacology* / Q000633:toxicity; D009281:Naphthalenes / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D020156:Salicylic Acid; D014012:Tinnitus / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology
D048588:Benzoxazines; C469526:Cnr2 protein, rat; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D020156:Salicylic Acid