Effects of the serotonin precursor, 5-hydroxytryptophan (5-HTP)
Funded in: 2020, 2021, 2022
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Problem: Loss of axons releasing chemicals contributes to impaired motor function
Target: Increased serotonin levels facilitate spinal cord excitability in individuals with injuries of differing chronicity and severity
Goal: Pharmacological modulation of neural excitability to improve motor recovery
Introduction: Following a spinal cord injury (SCI), the loss of axons from the brainstem to the spinal cord that release chemicals, such as serotonin, contributes to impaired motor function. Current therapeutic interventions do not take into account this obstacle to motor recovery.
Aim/Hypothesis: This proposal builds on findings in basic research models showing that the spinal cord adapts after a severe and chronic injury by increasing activity of the enzyme that breaks down the amino acid 5-hydroxytryptophan (5-HTP) into serotonin. The researchers aim to determine whether 5-HTP ingestion can increase serotonin levels below the lesion and facilitate spinal cord excitability in individuals with injuries of differing chronicity and severity.
Methods: Participants will visit the lab on four occasions where the scientists will examine the effects of a) 50mg 5HTP/carbidopa, b) 100mg 5-HTP/carbidopa, c) carbidopa only and d) placebo on neural excitability and muscle activity during a locomotor task in three groups of individuals; 1) those with subacute (6months-1year), motor complete (AIS A/B) SCI, 2) those with chronic (>2 years), motor complete SCI and 3) those with chronic, incomplete (AIS C/D) SCI.
Expected Results: Ingestion of 5-HTP will increase spinal excitability and facilitate muscle activity during a rhythmic, locomotor task, most likely through an increase in 5HT below the lesion. Specifically, sensory transmission should be decreased through 5HT1B/D receptor activation, motoneuron excitability increased (5HT2R) and rhythmic muscle activity will emerge (5HT2/5HT7R). Additionally, this pattern of effects will vary across the three participant groups as chronicity and injury severity should affect receptor plasticity and enzyme upregulation.
Potential Application: This study will improve the understanding of the pharmacological modulation of neural excitability after SCI. It will also provide insight into the potential of 5-HTP as an intervention used either alone, or in combination with activity-based training and/or neuromodulatory stimulation to improve motor recovery after SCI.