Effects of single administration of apomorphine on memory and monoamine metabolism: A dose related study

Abstract

In the present study, we have monitored dose dependent effects of apomorphine on learning and memory. 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., 0.5, 1.0, & 2.0 mg/ml/kg) on locomotion in a familiar environment (Skinner’s box) and memory in Morris water maze were investigated. Results show significantly enhanced activity in Skinner’s box in a dose dependant manner. Low dose (0.5 mg/ml/kg) of apomorphine impaired both short- as well as long-term memory while both high and moderate doses of the drug (1.0, & 2.0 mg/ml/kg) enhanced the cognitive profile in rats. However, the memory-enhancing effects of apomorphine at moderate (1.0 mg/ml/kg) dose were more pronounced as compared to high (2.0 mg/ml/kg) dose of the drug. Rats were decapitated on day 2. Whole brains of rats were collected and stored at -70°C. Biogenic amines (i.e., 5-Hydroxytryptamine; 5-HT and dopamine) and metabolites (i.e., Dihydroxyphenylacetic acid; DOPAC, Homovanillic acid; HVA & 5-Hydroxyindoleacetic acid; 5HIAA) were estimated by reverse phase High Performance Liquid Chromatography with electrochemical detector (HPLC-EC). Both low (0.5mg/ml/kg) as well as moderate (1.0mg/ml/kg) dose of apomorphine increased levels of dopamine, DOPAC, HVA, 5-HT and 5-HIAA. Whereas, high (4.0 mg/kg) dose of apomorphine increased levels of dopamine, DOPAC and HVA, while decreased 5-HT and 5-HIAA levels. Results would be helpful in elucidating memory enhancing effects of apomorphine at different doses and its implication for extending therapeutics in cognitive disorders.