Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.
BACKGROUND
Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system.


OBJECTIVE
The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC).


METHODS
The administration of a low dose of THC (0.3 mg/kg) produced clear anxiolytic-like responses in the light-dark box, as previously reported. The effects of the pretreatment with the CB(1) cannabinoid receptor antagonist, SR 141716A (0.5 mg/kg), or the micro -opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the delta-opioid receptor antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid receptor antagonist, nor-binaltorphimine (2.5 mg/kg) were evaluated on anxiolytic-like responses induced by THC.


RESULTS
SR 141716A completely blocked the anxiolytic-like response induced by THC, suggesting that this effect is mediated by CB(1) cannabinoid receptors. The micro -opioid receptor antagonist beta-funaltrexamine and the delta-opioid receptor antagonist naltrindole, but not the kappa-opioid receptor antagonist nor-binaltorphimine, abolished THC anxiolytic-like effects, suggesting an involvement of micro - and delta-opioid receptors in this behavioural response.


CONCLUSIONS
These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.
Laboratori de Neurofarmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universitat Pompeu Fabra, C/Doctor Aiguader 80, 08003 Barcelona, Spain.
Fernando
F
Berrendero
Rafael
R
Maldonado
D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D003624:Darkness; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004723:Endorphins / Q000502:physiology*; D008027:Light; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D000077285:Rimonabant
D014151:Anti-Anxiety Agents; D004723:Endorphins; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D013759:Dronabinol; C055382:naltrindole; D000077285:Rimonabant