TY - JOUR
T1 - Human motoneurone excitability is depressed by activation of serotonin 1A receptors with buspirone
AU - D'Amico, Jessica M
AU - Butler, Annie A
AU - Héroux, Martin E
AU - Cotel, Florence
AU - Perrier, Jean-François M
AU - Butler, Jane E
AU - Gandevia, Simon C
AU - Taylor, Janet L
N1 - © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - KEY POINTS: 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.ABSTRACT: 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.
AB - KEY POINTS: 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.ABSTRACT: 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.
KW - Adult
KW - Buspirone/pharmacology
KW - Double-Blind Method
KW - Electric Stimulation
KW - Electromyography
KW - Evoked Potentials, Motor/drug effects
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Motor Neurons/drug effects
KW - Muscle, Skeletal/drug effects
KW - Receptor, Serotonin, 5-HT1A/physiology
KW - Serotonin Receptor Agonists/pharmacology
KW - Spinal Cord/drug effects
KW - Ulnar Nerve/drug effects
KW - Young Adult
U2 - 10.1113/jp273200
DO - 10.1113/jp273200
M3 - Journal article
C2 - 27859267
SN - 0022-3751
VL - 595
SP - 1763
EP - 1773
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 5
ER -