Bhc. Westerink et al., Antipsychotic drugs induce similar effects on the release of dopamine and noradrenaline in the medial prefrontal cortex of the rat brain, EUR J PHARM, 361(1), 1998, pp. 27-33
In the present study we have compared the effects of the classical antipsyc
hotic drug haloperidol and four different atypical antipsychotics (clozapin
e, risperidone, olanzapine, ziprasidone) on extracellular levels of dopamin
e and noradrenaline in the medial prefrontal cortex (MPFC) of conscious rat
s. Haloperidol(10, 100 and 800 nmol/kg), clozapine (0.3, 1, 10 and 30 mu mo
l/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 subcu
taneously to rats. All compounds induced increases in dialysate levels of d
opamine and noradrenaline in the medial prefrontal cortex. The increases in
duced by the four antipsychotic agents in extracellular levels of dopamine
and noradrenaline displayed a striking co-variation both in dose and time.
A similar cc-variation was seen in the decrease of dopamine and noradrenali
ne, after administration of a low dose (30 nmol/kg, s.c.) of the dopamine D
-2/3 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 rele
ase of dopamine and noradrenaline in the medial prefrontal cortex. The mech
anism of action of this interaction, that might be of importance for a bett
er understanding of the mechanism of action of antipsychotic drugs, is disc
ussed. (C) 1998 Elsevier Science B.V. All rights reserved.