Quantitative assessment of dopamine D2 antagonist activity using invertebrate ( Planaria) locomotion as a functional endpoint

Abstract

Introduction: Dopaminergic ligands, including drugs of abuse, modulate the locomotor activity of planarians and induce characteristic abnormal patterns of motility at high doses. It has been presumed that the effect is related to dopamine receptors based on ligand specificity and effects on second messenger levels. However, to date, the measured changes have been mostly qualitative in nature and it is not completely clear that the effect is related to stereospecific receptor mechanisms. Methods: The present study addressed these issues by devising a convenient and sensitive metric (locomotor velocity, pLMV) and applied the method to test Planaria enantiomer-sensitivity to a dopamine D2-receptor antagonist. Results: pLMV was remarkably constant over the observation period and established a stable baseline against which to study and quantitate pharmacologic intervention. Further, S(−)-sulpiride at low doses (10 −10 to 10 −8 M) attenuated pLMV in a dose-dependent manner, but R(+)-sulpiride was only 1/25th as potent. Discussion: The new methodology thus provides a method for quantifying actions of D2 ligands in a simple in vivo system.