Clozapine blocks dopamine, 5-HT2 and 5-HT3 responses in the medial prefrontal cortex: an in vivo microiontophoretic study

Clozapine is an atypical antipsychotic drug active on both positive and neg ative symptoms of schizophrenia which has a unique serotonergic and dopamin ergic profile. Given the putative role of the medial prefrontal cortex (mPF C) in negative symptoms of schizophrenia, the aim of this study was to asse ss the effects of clozapine on the dopamine- and serotonin-responsive neuro ns in that particular brain structure. D-1 and D-2 agonists (SKF 38393 and quinpirole) as well as 5-HT2 and 5-HT3 agonists (1-(2,5-dimethoxy-4iodophen yl)-2-aminopropane, DOI, and phenylbiguanide) were applied by microiontopho resis alone and concurrently with clozapine while recording extracellularly mPFC neurons. Dopamine ejections inhibited firing activity while D-1 and D -2 agonists were ineffective. Clozapine did not change basal firing by itse lf, but was able to suppress the inhibition produced by dopamine and by the 5-HT2/5-HT3 receptor agonists. It is concluded that clozapine at the mPFC level exerts a complex modulatory activity on dopamine receptors, that is d irectly at the dopaminergic receptors and through 5-HT receptors on the sam e neurons. (C) 1999 Elsevier Science B.V. All rights reserved.