Effect of fluoxetine on neuromuscular function in acetylcholinesterase (AChE) knockout mice.
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.
Différenciation Cellulaire et Croissance UMR 866 INRA, Université Montpellier 1 & 2 Montpellier, 2 place Vila, Montpellier, France.
Christelle
C
Bertrand
Beatrice
B
Bonafos
Maud
M
Tremblay
Arnaud
A
Ferry
Arnaud
A
Chatonnet
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005473:Fluoxetine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000110:Acetylcholinesterase; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors