In vivo antagonism of the behavioral responses to L-3-,4-dihydroxyphenylalanine by L-3-,4-dihydroxyphenylalanine cyclohexyl ester in conscious rats.
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.
Matsushita
Naoko
N
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Misu
Yoshimi
Y
Goshima
Yoshio
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007980:Levodopa / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D006834:Hydrazines; D017448:Receptors, Dopamine D2; C110321:levodopa cyclohexyl ester; D019257:Quinpirole; D007980:Levodopa; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine