Anxiolytics may promote locomotor function recovery in spinal cord injury patients

Pierre A Guertin

Neuroscience Unit, Laval University Medical Center (CHUL), Quebec City, Canada

Abstract: Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI). Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR) ligands such as 5-HTR_1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously), some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx) rodents. Using ‘knock-out’ mice (eg, 5-HTR₇-/-) and selective antagonists, it has been clearly established that both 5-HTR_1A and 5-HTR₇ were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR_1A agonist) in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR_1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.

Keywords: 5-HT agonists, anxiolytics, locomotion, SCI