title: Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats.
abstract: Tardive dyskinesia (TD) is a debilitating side effect of long-term treatment with neuroleptics with an unclear pathophysiologic basis. It has been proposed that TD may be a result of neuroleptic-induced oxidative stress. To investigate this hypothesis, we studied if neuroleptic-induced oral dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL significantly increased the level of oral dyskinesias, and the increase persisted for 12 weeks after drug withdrawal. Cotreatment with CoQ10 did not attenuate the development of HAL-induced oral dyskinesia. Despite adequate absorption of orally administered CoQ10, shown by the increased serum levels of CoQ10, no increase of either CoQ10 or coenzyme Q9 was detected in the brain. These results suggest that cotreatment with CoQ10 does not inhibit the development of HAL-induced oral dyskinesias in rats, and that further studies seem to be needed in order to clarify the pharmacokinetics of CoQ10 in rats.
authors.affiliation: Department of Physiology, University of Bergen, Norway.
authors.forename: O A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: H A
authors.initials: HA
authors.lastname: Jørgensen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D003067:Coenzymes; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control*; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D003067:Coenzymes; D014451:Ubiquinone; C024989:coenzyme Q10; D006220:Haloperidol