Clozapine-induced dopamine levels in the rat striatum and nucleus accumbens are not affected by muscarinic antagonism

The effect of the muscarinic antagonist, scopolamine, was examined for a ch ange in the increase in extracellular dopamine, dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA), i nduced by haloperidol or clozapine in the striatum and nucleus accumbens of anaesthetised and awake rats,:monitored using in vivo cerebral microdialys is. Rats received scopolamine (1 mg kg(-1); s.c.) or vehicle followed by ha loperidol (1 mg kg(-1); s.c.) or clozapine (20 mg kg(-1); s.c.). Dopamine, DOPAC, HVA and 5-HIAA overflow into striatal or accumbens perfusates was de termined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Scopolamine failed to modify the clozapine- or halope ridol-induced efflux of dopamine or its metabolites in either the striatum or nucleus accumbens following systemic administration in anaesthetised or awake rats. Although pretreatment with scopolamine tended to produce a smal ler increase in the clozapine-induced efflux of DOPAC in striatal perfusate s than following clozapine treatment alone, this was not statistically sign ificant. Furthermore, local infusion of scopolamine (100 mu M) with clozapi ne (1 mM) via the microdialysis probe did not attenuate the elevated efflux of dopamine observed following clozapine alone, in either the striatum or nucleus accumbens, in anaesthetised rats. This treatment did prevent the cl ozapine-induced increase in DOPAC and HVA in the striatum but not the nucle us accumbens. Carbachol (50 mu M) infused into the dorsolateral striatum or nucleus accumbens raised extracellular dopamine levels 200% and 150%, resp ectively above baseline. Our data suggest that the increased efflux of dopa mine and its metabolites in the rat basal ganglia following clozapine admin istration is not significantly dependent upon the interaction of clozapine with muscarinic receptors. (C) 1998 Elsevier Science B.V. All rights reserv ed.