title: Human motoneurone excitability is depressed by activation of serotonin 1A receptors with buspirone.
abstract: In the adult turtle spinal cord, action potential generation in motoneurones is inhibited by spillover of serotonin to extrasynaptic serotonin 1A (5-HT1A) receptors at the axon initial segment. We explored whether ingestion of the 5-HT1Areceptor partial agonist, buspirone, decreases motoneurone excitability in humans. Following ingestion of buspirone, two tests of motoneurone excitability showed decreases. F-wave areas and persistence in an intrinsic muscle of the hand were reduced, as was the area of cervicomedullary motor evoked potentials in biceps brachii. Our findings suggest that activation of 5-HT1Areceptors depresses human motoneurone excitability. Such a depression could contribute to decreased motoneurone output during fatiguing exercise if there is high serotonergic drive to the motoneurones.
  
  
  
  Intense serotonergic drive in the turtle spinal cord results in serotonin spillover to the axon initial segment of the motoneurones where it activates serotonin 1A (5-HT1A) receptors and inhibits generation of action potentials. We examined whether activation of 5-HT1Areceptors decreases motoneurone excitability in humans by determining the effects of a 5-HT1Areceptor partial agonist, buspirone, on F waves and cervicomedullary motor evoked potentials (CMEPs). In a placebo-controlled double-blind study, 10 participants were tested on two occasions where either placebo or 20 mg of buspirone was administered orally. The ulnar nerve was stimulated supramaximally to evoke F waves in abductor digiti minimi (ADM). CMEPs and the maximal M wave were elicited in biceps brachii by cervicomedullary stimulation and brachial plexus stimulation, respectively. Following buspirone intake, F-wave area and persistence, as well as CMEP area, were significantly decreased. The mean post-pill difference in normalized F-wave areas and persistence between buspirone and placebo days was -27% (-42, -12; 95% confidence interval) and -9% (-16, -2), respectively. The mean post-pill difference in normalized CMEP area between buspirone and placebo days showed greater variation and was -31% (-60, -2). In conclusion, buspirone reduces motoneurone excitability in humans probably via activation of 5-HT1Areceptors at the axon initial segment. This has implications for motor output during high drive to the motoneurones when serotonin may spill over to these inhibitory receptors and consequently inhibit motoneurone output. Such a mechanism could potentially contribute to fatigue with exercise.
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.
authors.forename: Jessica M
authors.identifier: 0000-0002-3487-0712
authors.initials: JM
authors.lastname: D'Amico
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: Annie A
authors.initials: AA
authors.lastname: Butler
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Héroux
authors.affiliation: Queensland Brain Institute, Brisbane, QLD, Australia.
authors.forename: Florence
authors.initials: F
authors.lastname: Cotel
authors.affiliation: University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jean-François M
authors.identifier: 0000-0002-9189-3574
authors.initials: JM
authors.lastname: Perrier
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Butler
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Gandevia
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: Janet L
authors.identifier: 0000-0001-8976-5162
authors.initials: JL
authors.lastname: Taylor
mesh_terms: D000328:Adult; D002065:Buspirone / Q000494:pharmacology*; D004311:Double-Blind Method; D004558:Electric Stimulation; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D014459:Ulnar Nerve / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D002065:Buspirone
keywords: 5HT1A receptors; F waves; central fatigue; cervicomedullary motor evoked potentials; motoneurones; muscle fatigue; serotonin