Acute and chronic effects of clozapine on cholinergic transmission in cultured mouse superior cervical ganglion neurons

Autor:	Suzann M. Babb, Wei-Dong Yao, Qi Ma, Taixiang Saur, Bruce M. Cohen, Edgar A. Buttner
Rok vydání:	2016
Předmět:	0301 basic medicine Superior cervical ganglion medicine.drug_class Postsynaptic Current Atypical antipsychotic Superior Cervical Ganglion Pharmacology Synaptic Transmission Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Postsynaptic potential Genetics Animals Medicine Clozapine Cells Cultured Neurons business.industry Excitatory Postsynaptic Potentials 030104 developmental biology Nicotinic agonist Excitatory postsynaptic potential Cholinergic business Neuroscience 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug
Zdroj:	Journal of Neurogenetics. 30:297-305
ISSN:	1563-5260 0167-7063
DOI:	10.1080/01677063.2016.1229779
Popis:	Cholinergic dysfunction contributes to cognitive deficits associated with various neuropsychiatric disorders, including schizophrenia. The atypical antipsychotic clozapine improves cognitive function in patients with schizophrenia, possibly through modulation of the cholinergic system. However, little is known about specifics of the underlying mechanisms. In this study, we investigated the acute and chronic effects of clozapine on cholinergic synaptic transmission in cultured superior cervical ganglion (SCG) neurons. Spontaneous excitatory postsynaptic currents (sEPSCs) were readily detected in this preparation and were reversibly inhibited by the nicotinic receptor antagonist d-tubocurarine, confirming that the synaptic responses were primarily mediated by nicotinic receptors. Bath application of clozapine at therapeutic concentrations rapidly and reversely inhibited both the amplitude and frequency of sEPSCs in a concentration dependent manner, without changing either rise or decay time, suggesting that clozapine effects have both presynaptic and postsynaptic origins. The acute effects of clozapine on sEPSCs were recapitulated by chronic treatment of SCG cultures with similar concentrations of clozapine, as clozapine treatment for four days reduced the frequency and amplitude of sEPSCs without affecting their kinetics. Cell survival analysis indicated that SCG neuron cell counts after chronic clozapine treatment were comparable to the control group. These results demonstrate that therapeutic concentrations of clozapine suppress nicotinic synaptic transmission in SCG cholinergic synapses, a simple in vitro preparation of cholinergic transmission.
Databáze:	OpenAIRE
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