Ontogenic variations in responses to L-DOPA and monoamine receptor-stimulating agents.

Abstract

The spontaneous motor activity, overt behavioral responses, and concentration of NA and DA in the brain were studied in young rats at different postnatal ages following the administration of l-DOPA (100 mg/kg) or NA and DA receptor-stimulating or blocking agents. l-DOPA induced marked hyperactivity even at one day of age and the duration of the l-DOPA-induced hyperactivity and increase in NA and DA concentrations in the brain decreased with ontogenic development. At 21 days, the apparent behavioral response to l-DOPA was one of depression rather than marked excitation. Pretreatment of 21 day-old animals with MK-486, a peripheral decarboxylase inhibitor, produced excitation with aggressive responses, whereas in younger animals the effect of this drug was only to lengthen the duration of the response. It was concluded that not until around 21 days of age does the capacity of the peripheral decarboxylase become a major factor in determining the behavioral response to l-DOPA. Clonidine, a NA-receptor-stimulating agent elicited behavioral rssponses from one day of age similar to the responses observed after l-DOPA. A response to apomorphine, a DA-receptor-stimulating agent, was not readily observed until 4 days of age and then the response was rather variable. Marked stereotyped behavior was not observed in response to apomorphine until 21 days of age. This difference between clonidine and apomorphine stimulation was considered to suggest that NA receptors may develop at an earlier age than DA receptors.