Effect of fluoxetine on neuromuscular function in acetylcholinesterase (AChE) knockout mice - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Conference Papers Year : 2008

Effect of fluoxetine on neuromuscular function in acetylcholinesterase (AChE) knockout mice

Abstract

Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. The causal mutations have been described in number of cases. The slow channel myasthenic syndrome (slow-channel- CMS) results in a marked prolongation of channel opening in stimulated receptors (nAChR) and the end plate acetylcholinesterase (AChE) deficiency congenital myasthenic syndrome (ColQ-CMS) results in an increased action of acetylcholine (ACh) at the synapse. Anticholinesterase medication is detrimental in these cases. The successful treatment of slow-channel-CMS patients with the antidepressant serotonin re-uptake inhibitor fluoxetine has been reported. At high concentration it has a non-depolarizing effect on nicotinic receptors. This led us to the idea that fluoxetine could protect AChR from a relative excess of ACh. We investigated the possible use of fluoxetine as treatment in the AChE KO mouse. Treatment at 6 mg/kg from 3 weeks to 2 months increased slightly the daily weight gain but not the final weight at 2 months in AChE−/− mice. Isometric force production of Tibialis anterior in response to electric nerve stimulation was measured in situ in AChE−/− and wild type mice treated or not by fluoxetine. The results show that the maximum twitch force in response to a single nerve stimulation, the maximal tetanic force (P0) in response to repetitive nerve stimulation and the tetanic fade are not changed in AChE−/− mice treated with fluoxetine versus control AChE−/− mice.

Dates and versions

hal-02758520 , version 1 (04-06-2020)

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Cite

Christelle Bertrand, Béatrice Bonafos, Maud Tremblay, Arnaud Ferry, Arnaud Chatonnet. Effect of fluoxetine on neuromuscular function in acetylcholinesterase (AChE) knockout mice. 9. International Meeting on Cholinesterases, May 2007, Suzhou, China. ⟨10.1016/j.cbi.2008.04.002⟩. ⟨hal-02758520⟩
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