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 15min and 40min post injection). Animals were decapitated 1 hr post apomorphine injection and whole brains of animals were collected and stored at -70ο 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 nonsignificant 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.