title: Effects of apomorphine on locomotive activity and monoamine metabolism: a dose related study.
abstract: We have monitored dose dependent effects of apomorphine on motor activity and monoamine metabolism. Behavioral sensitization and craving, which develop upon repeated treatment with dopamine receptor agonist apomorphine, are major limitations of the therapeutic use of apomorphine in Parkinson's patients. Effects of single (intraperitoneal) injection of apomorphine at different doses (i.e., 1.0, 2.0 & 4.0 mg/kg) on exploration in a novel environment (open field) and locomotion in a familiar environment (home cage) were investigated. Results show significantly enhanced activity in home cage (monitored 5min post injection) in a dose dependent manner. However, no significant influence of apomorphine on exploration of open field was observed in the present study (monitored 15 min and 40 min post injection). Animals were decapitated 1 hr post apomorphine injection and whole brains of animals were collected and stored at -70°C. Biogenic amines (i.e., 5-Hydroxytryptamine and dopamine) and metabolites (i.e., Dihydroxyphenylacetic acid, Homovanillic acid & 5-Hydroxyindoleacetic acid) were estimated by reverse phase High Performance Liquid Chromatography with electrochemical detector (HPLC-EC). Effect of low (1.0mg/kg) dose of apomorphine was found to be non-significant on 5-Hydroxytryptamine (5-HT), 5-Hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) levels. Moderate (2.0 mg/kg) dose of drug increased (p<0.05) levels of Homovanillic acid (HVA). Whereas, high (4.0 mg/kg) dose of apomorphine decreased Dihydroxyphenylacetic acid (DOPAC) levels. Results could be helpful in elucidating the effect of apomorphine at different doses and its implication for extending therapeutics in Parkinson's and related disorders.
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan. huma_biochemist@yahoo.com
authors.forename: Huma
authors.initials: H
authors.lastname: Ikram
authors.forename: Shoaib
authors.initials: S
authors.lastname: Ahmad
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D001058:Apomorphine