Quercetin, a bioflavonoid, reverses haloperidol-induced catalepsy.
Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. Unfortunately their use is often associated with distressing side effects involving the extrapyramidal tract, such as Parkinsonism and tardive dyskinesia. Neuroleptic-induced catalepsy has long been used as a model for extrapyramidal side effects such as Parkinsonian-like bradykinesia associated with antipsychotic use in humans. In the present study, haloperidol (2 mg/kg i.p.) was administered to mice to induce catalepsy and cataleptic response was measured for the next 4 h at 1 h intervals. Haloperidol treatment in mice induced a strong cataleptic state within 1 h of injection, reaching a maximal plateau after 2 h and lasting for 4 h. Vehicle-treated animals did not display catalepsy as they remained less than 5 sec on the bar at each time point. Pretreatment with quercetin dose-dependently (25-100 mg/kg p.o.) reduced the catalepsy score in haloperidol-treated animals. A dose response study of quercetin showed a characteristic U-shaped response curve, with maximum suppression observed at a dose of 100 mg/kg. On increasing the dose of quercetin to 300 mg/kg, no statistically significant difference in catalepsy score was observed compared with the haloperidol-treated group. In conclusion, the findings of the present study strongly suggest that quercetin can be screened as a potential drug candidate or as an adjuvant for the treatment of neuroleptic-induced extrapyramidal side effects.
Naidu
P S
PS
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002375:Catalepsy / Q000139:chemically induced* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D011794:Quercetin / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D011794:Quercetin; D006220:Haloperidol