Antipsychotic drugs induce similar effects on the release of dopamine and noradrenaline in the medial prefrontal cortex of the rat brain.
In the present study we have compared the effects of the classical antipsychotic drug haloperidol and four different atypical antipsychotics (clozapine, risperidone, olanzapine, ziprasidone) on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex (MPFC) of conscious rats. Haloperidol (10, 100 and 800 nmol/kg), clozapine (0.3, 1, 10 and 30 micromol/kg), risperidone (100, 500 and 5000 nmol/kg), olanzapine (10, 100 and 500 nmol/kg) and ziprasidone (10, 100 and 1000 nmol/kg) were administered subcutaneously to rats. All compounds induced increases in dialysate levels of dopamine and noradrenaline in the medial prefrontal cortex. The increases induced by the four antipsychotic agents in extracellular levels of dopamine and noradrenaline displayed a striking co-variation both in dose and time. A similar co-variation was seen in the decrease of dopamine and noradrenaline, after administration of a low dose (30 nmol/kg, s.c.) of the dopamine D2/3 receptor agonist (+)-7-hydroxy-2-(N,N-di-n-propylamino) tetralin ((+)-7-OH-DPAT). It is concluded that there is a close coupling between the release of dopamine and noradrenaline in the medial prefrontal cortex. The mechanism of action of this interaction, that might be of importance for a better understanding of the mechanism of action of antipsychotic drugs, is discussed.
Westerink
B H
BH
University Center for Pharmacy, Department of Medicinal Chemistry, Groningen, The Netherlands. westerink@farm.rug.nl
de Boer
P
P
de Vries
J B
JB
Kruse
C G
CG
Long
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018967:Risperidone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D010879:Piperazines; D013764:Tetrahydronaphthalenes; D013844:Thiazoles; D001569:Benzodiazepines; D010890:Pirenzepine; C092292:ziprasidone; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine; D009638:Norepinephrine