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Recovery of Locomotor Function with Combinatory Drug Treatments Designed to Synergistically Activate Specific Neuronal Networks

[ Vol. 16 , Issue. 11 ]


Pierre A. Guertin   Pages 1366 - 1371 ( 6 )


Spinal cord injury (SCI) is a devastating condition generally leading to a permanent and irreversible loss of sensory and motor functions. We have identified recently a number of serotonergic, adrenergic and dopaminergic receptor agonists or precursors that can acutely elicit some motor and locomotor-like movements in completely spinal cordtransected (thoracic level) animals. However, only partial central network-activating effects were found with single molecules since none administered separately could elicit weight-bearing and functional stepping movements in Tx animals. In turn, a recent breakthrough revealed that full spinal locomotor network-activating effects may be induced with synergistic drug combinations. Indeed, specific cocktails comprising some of these agonists and precursors were found, indeed, to powerfully generate weight-bearing stepping with plantar foot placement in untrained, non-assisted and non-sensorystimulated Tx mice. This significant finding provides clear evidence suggesting that combinatorial approaches based on drug-drug synergistic interactions may constitute innovative solutions for the design and development of novel pharmacological therapies in the field of SCI and related neurological disorders.


Spinal cord, SCI, central pattern generator, CPG, locomotion, dopamine, serotonin, L-DOPA, mice


Laval University Medical Center (CHUL–CHUQ), Neuroscience Unit, RC-9800, 2705 Laurier Blvd, Quebec City, Quebec, G1V 4G2, Canada.

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