Methanandamide attenuates cocaine-induced hyperthermia in rats by a cannabinoid CB sub(1)-dopamine D sub(2) receptor mechanism

• Published in: Brain research 2009-03, Vol.1260, p.7-14
• Main Authors: Rasmussen, BA, Kim, E, Unterwald, E M, Rawls, S M
• Format: Article
• Language: English
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2008.12.078

Evidence implicates anandamide in dopamine-related cocaine function. In the present study, we investigated the effect of methanandamide (5 mg/kg, i.p.), a stable anandamide analog, on the hyperthermia and hyperactivity induced by a fixed dose of cocaine (15 mg/kg, i.p.). Cocaine administered to rats produced hyperthermia and hyperactivity whereas methanandamide was ineffective. For combined administration, methanandamide attenuated the hyperthermia, but not hyperactivity, induced by cocaine. The effect of methanandamide was abolished by pretreatment with a cannabinoid CB sub(1) receptor antagonist, SR141716A (5 mg/kg, i.p.), or dopamine D sub(2) receptor antagonist, S(-)-raclopride (5 mg/kg, i.p.) but not by capsazepine (40 mg/kg, i.p.), a transient receptor potential vanilloid 1 cation channel antagonist. Methanandamide also attenuated the hyperthermia caused by a dopamine D sub(1) receptor agonist, SKF 38393 (10 mg/kg, s.c.), indicating that it reduces hyperthermia produced by dopamine D sub(1) receptor activation. URB597 (0.25 mg/kg, i.p.), an inhibitor of anandamide metabolism, did not alter cocaine-induced hyperthermia. Our results demonstrate that methanandamide activates cannabinoid CB sub(1) receptors to attenuate cocaine-induced hyperthermia, and that dopamine D sub(2) receptor activation plays a permissive role in the thermoregulatory effects of methanandamide.