Anxiolytics may promote locomotor function recovery in spinal cord injury patients

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-HTR(7)-/-) and selective antagonists, it has been clearly established that both 5-HTR(1A) and 5-HTR(7) 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.