Microelectrode arrays (MEAs) with cultured neuronal networks are highly suitable to quantify neuroactive activity and neurotoxicity of applied substances.

Multiparametric characterization of functional alterations of in vitro-neuronal network activity by different typical and atypical antipsychotics.

To identify differential effects of antipsychotics on spontaneous neuronal network activity as a functional readout.

Cultured networks of dissociated cortical cells of postpartal mice coupled to MEAs were exposed to increasing doses of aripiprazole, clozapine, haloperidol, olanzapine, raclopride, and risperidone.

We found a concentration-dependent inhibition of firing patterns for all substances except olanzapine. All other substances mediated a concomitant irreversible suppression of burst and spike rates, a decrease of the burst duration and the number of spikes in bursts as well as dose-dependent network desynchronization (decrease of Cohen's kappa). The comparison of the different antipsychotics with regard to their half-maximal effective dose values (EC-50) for inhibiting the spike rate yielded an increasing order of EC50 values, i.e. a declining order of toxic potency, of aripiprazole (8.77 μM) < clozapine (9.36 μM) < haloperidol (9.77 μM) < risperidone (15.9 μM) < raclopride (22.7 μM). No significant correlations were identified between EC50 values of the distinct antipsychotics and their binding affinity to the dopamine D(2), the serotonin 5-HT(1A), 5-HT(2A), 5-HT(2C), and the M(1) and M(2) muscarinic acetylcholine receptors.

In MEAs, a dose-dependent neurotoxic effect of typical and atypical antipsychotics alike occurred at supratherapeutic doses via a yet unknown mechanism that did not involve actions on major receptor targets of these compounds.

The authors have not supplied their declaration of competing interest.