Caffeine inhibits Levodopa-Induced Potentiation of Haloperidol-Induced Catalepsy and Tardive Dyskinesia in Balb/ C Mice

ABSTRACTCaffeine is a nonspecific adenosine receptor antagonist useful in treatment of Parkinson’s disease (PD). Haloperidol induced catalepsy and vacuous chewing movements in laboratory animals are inhibited by caffeine. There is a report that repeated administrations of levodopa produced increased formation of 6-OHDA in Balb/C mice which aggravates the extrapyramidal effects of neuroleptics. Chronic administration of levodopa is reported to alter mitochondrial respiratory chain activity in rats and this activity is thought to be related to an oxidative stress and is responsible for progression of PD. We therefore studied the effect of repeated administration of levodopa (with carbidopa) on haloperidol induced catalepsy and vacuous chewing movement (VCMs) and the modifications by caffeine. We also studied effect of chronic levodopa on SOD, Catalase, lipid peroxidation, and reduced glutathione levels in mice. In the experiment to study the effect of levodopa + carbidopa (LD+CD; 6:0.6 mg/kg i.p.), with or without caffeine (10 & 20 mg/kg i.p.), administered for 27 days and the duration of catalepsy in 5 min interval was recorded every 30 min till 180 min. The effect on the biochemical parameters was assessed on the 27th day. Haloperidol induced catalepsy and VCMs intensified gradually and simultaneous treatment with LD + CD potentiated both catalepsy and VCMs. Caffeine in both the doses significantly reduced duration of catalepsy and number of VCMs in all the treated groups. Caffeine also reversed the effect of haloperidol given with or without LD+CD on the enzyme markers of the stress significantly. The results suggest involvement of oxidative stress in exaggeration of pharmacological effects of haloperidol and their inhibition by caffeine.       Keywords: Caffeine, haloperidol, catalepsy, vacuous chewing movements, stress