Recovery of locomotor function with combinatory drug treatments designed to synergistically activate specific neuronal networks.
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 cord-transected (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-sensory-stimulated 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.
Guertin
Pierre A
PA
Laval University Medical Center (CHUL - CHUQ), Neuroscience Unit, RC-9800, 2705 Laurier Blvd, Quebec City, Quebec, G1V 4G2, Canada. Pierre.Guertin@crchul.ulaval.ca
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D012046:Rehabilitation; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy
D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D007980:Levodopa; D004298:Dopamine