Regulation of dopamine release and metabolism in rat striatum in vivo: effects of dopamine receptor antagonists.
1. The acute effects of some of typical and atypical antipsychotic drugs on the dopamine release and metabolism in the dorsal striatum of freely moving rats were studied using transcerebral microdialysis technique. 2. Classical neuroleptic drugs haloperidol (0.05, 0.1 and 0.2 mg/kg), thioproperazine (0.1, 0.2 and 0.4 mg/kg) and spiperone (0.02, 0.04 and 0.07 mg/kg) administered i.p. induced pronounced elevation of extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) up to 250-300% to basal level while producing less increase in that of dopamine (DA) (up to 150-170%). 3. Atypical neuroleptics clozapine and thioridazine (both 2, 5 and 20 mg/kg) increased striatal DA release and DOPAC level approximately at the same degree (maximally up to 200% and 160%, respectively). 4. Dopamine D3 receptor and autoreceptor preferring antagonists (+)-UH232 and (+)-AJ76 (both 4, 7 and 14 mg/kg) more potently increased DA release in comparison with DOPAC dialysate level (+)-AJ76 elevated DA level maximally up to 330%, DOPAC-up to 250%). 5. The features of typical and atypical neuroleptics in preferential action on DA release or DOPAC output were observed in all doses of the drugs studied. 6. The ability of the drugs to affect preferentially DA release or DOPAC extracellular level in rat striatum correlates to their relative affinities at D3 and D2 DA receptors. 7. It is concluded that typical and atypical antipsychotic drugs might be clearly distinguished on the basis of their ability to affect preferentially DA synthesis/metabolism or release in rat dorsal striatum in vivo.
Rayevsky
K S
KS
Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.
Gainetdinov
R R
RR
Grekhova
T V
TV
Sotnikova
T D
TD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid