In vivo antagonism of the behavioral responses to L-3-,4-dihydroxyphenylalanine by L-3-,4-dihydroxyphenylalanine cyclohexyl ester in conscious rats

Abstract

To establish the neurotransmitter role(s) of L-3,4-dihydroxyphenylalanine (DOPA) in its own right, we attempted to clarify whether i.p. injection of a DOPA antagonist, DOPA cyclohexyl ester (CHE), would antagonize the behavioral responses of conscious rats to DOPA in the presence of 3-hydroxybenzylhydrazine (NSD-1015) (100 mg/kg i.p.), a central aromatic L-amino acid decarboxylase (AADC) inhibitor. DOPA-CHE (40, 60 and 100 mg/kg) elicited a dose-dependent partial antagonism against the increase in locomotor activity induced by DOPA (100 mg/kg i.p.). A low dose of DOPA-CHE (10 mg/kg) elicited full antagonism against the potentiating effect of a non-effective dose of DOPA (20 mg/kg) on the increase in locomotor activity induced by a dopamine D 2 agonist quinpirole (0.3 mg/kg s.c.). DOPA-CHE (100 mg/kg) elicited full antagonism against licking behavior induced by DOPA (100 mg/kg). We confirmed that DOPA (100 mg/kg) increased the striatal dopamine content but elicited no effect on locomotor activity in the presence of benserazide (50 mg/kg i.p.), a peripheral AADC inhibitor. DOPA also increased the dopamine content in the presence of NSD-1015 to a maximal degree similar to that in the presence of benserazide. Thus, we conclude that DOPA-CHE is a suitable DOPA antagonist that would be available under in vivo experimental conditions. DOPA plays a role in the neuromodulation of behavior.