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Typical and atypical antipsychotics alter acetylcholinesterase activity and ACHE expression in zebrafish (Danio rerio) brain.

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Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul Avenida Ipiranga, Porto Alegre, RS, Brazil


Antipsychotic agents are widely used for the treatment of psychotic symptoms in patients with several brain disorders. Antipsychotic drugs principally affect dopamine systems with the newer ones also affecting serotonin, norepinephrine, and histamine systems. Other transmitter systems can be involved with selected antipsychotic drugs but effects on cholinergic system are less known. Considerable evidence has shown that complex interactions between dopaminergic and cholinergic systems are critical for the proper regulation of motor control and memory. These neurotransmitter systems have been studied in zebrafish, which has recently become a focus of neurobehavioral studies. Therefore, we have evaluated the in vitro and in vivo effects of sulpiride, olanzapine, and haloperidol on acetylcholinesterase activity and ache expression pattern in zebrafish brain. For in vitro studies, all drugs were able to promote a decrease on acetylcholinesterase activity. For in vivo studies, olanzapine and sulpiride exposure did not change acetylcholinesterase activity. In contrast, this enzyme activity was significantly increased at 5 and 9 microM haloperidol (29.9% and 20.4%, respectively). Haloperidol exposure was able to increase acetylcholinesterase mRNA transcripts. These findings have suggested that the alterations in zebrafish acetylcholinesterase could reveal molecular mechanisms related to cholinergic signaling induced by antipsychotic treatment.

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