Stimulation of brain dopamine autoreceptors by remoxipride administration in reserpine-treated male rats.
Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg-1, -18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg-1 -30 min). Remoxipride 0.8, 3.2 or 12.8 mg kg-1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.
Ahlenius
S
S
Department of Behavioral Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Ericson
E
E
Wijkström
A
A
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D004563:Electrochemistry; D006220:Haloperidol / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*; D017330:Remoxipride / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013469:Sulpiride / Q000494:pharmacology
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D011954:Receptors, Dopamine; D017330:Remoxipride; D004295:Dihydroxyphenylalanine; D013469:Sulpiride; D012110:Reserpine; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D004298:Dopamine