A role for central cannabinoid and opioid systems in peripheral delta 9-tetrahydrocannabinol-induced analgesia in mice.
delta 9-tetrahydrocannabinol elicits analgesia in rodents by both spinal and supraspinal mechanisms. Pharmacological data point to a link between cannabinoids and the opioid system. The lack of specific cannabinoid receptor antagonists has hindered the investigation of the physiological relevance of the cannabinoid system in nociception control. In this work we characterized the effect of the new cannabinoid receptor antagonist, SR-141,716 A (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3- pyrazolecarboxamide hydrochloride), on delta 9-tetrahydrocannabinol-induced analgesia. pA2 values in the tail-flick and in lick and jump responses in the hot-plate tests were 9.59, 8.72 and 10.21, respectively. Slope values of pA2 plots were not different from -1 indicating competitive antagonism. The involvement of the opioid system in delta 9-tetrahydrocannabinol-induced analgesia was investigated by using naloxone as well as delta (naltrindole)- and kappa (nor-binaltorphimine)-opioid receptor antagonists. Intrathecal nor-binaltorphimine antagonized the effect of delta 9-tetrahydrocannabinol. The effect of delta 9-tetrahydrocannabinol was also blocked by administration of dynorphin A-(1-8) antiserum in the same test.
Reche
I
I
Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense de Madrid, Spain.
Fuentes
J A
JA
Ruiz-Gayo
M
M
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D004399:Dynorphins / Q000276:immunology / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D000077285:Rimonabant
D000700:Analgesics; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011957:Receptors, Opioid; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D013759:Dronabinol; D000077285:Rimonabant