Neurochemical and behavioral effects of m-CPP in a rat model of tardive dyskinesia.
Present study was designed to monitor the responsiveness of 5HT (5-Hydroxytryptamine) -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP (meta-Chlorophenyl piperazine) were monitored 48 h after withdrawal from repeated (twice a day for 5 week) administration of haloperidol (at the dose of 1 mg/kg). Vacuous chewing movements (VCMs) were monitored on weekly basis. Two days after withdrawal, animals were injected with saline (1 ml/kg of body weight) or m-CPP (3 mg/kg of body weight). Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals were then decapitated (4 h post injection) to collect dorsal striatum (DS) samples for the neurochemical analysis by HPLC-EC (High Performance Liquid Chromatography with Electrochemical detection) method. Results from the present study showed significant hypolocomotive effect of m-CPP (p<0.05) in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly (p<0.05) decreased 5-HIAA (5-Hydroxyindol acetic acid) in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia (TD). These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics.
Ikram
Huma
H
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi-75250, Pakistan. huma_biochemist@yahoo.com
Samad
Noreen
N
Haleem
Darakhshan Jabeen
DJ
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D004563:Electrochemistry; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D058826:Serotonin 5-HT2 Receptor Agonists
D014150:Antipsychotic Agents; D010879:Piperazines; D058826:Serotonin 5-HT2 Receptor Agonists; D006897:Hydroxyindoleacetic Acid; D006220:Haloperidol; C015068:1-(3-chlorophenyl)piperazine