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

[ Vol. 16 , Issue. 11 ]

Author(s):

Pierre A. Guertin   Pages 1366 - 1371 ( 6 )

Abstract:


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.

Keywords:

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

Affiliation:

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



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