Chemical activation of the mesencephalic locomotor region.

Electrical stimulation of the mesencephalic locomotor region (MLR) in the precollicular-postmammillary transected cat is known to induce controlled locomotion on a treadmill. We have been able to induce and block locomotion in this preparation by using localized infusions of transmitters and their agonists and antagonists. Infusions of the GABA antagonists bicuculline and picrotoxin into the MLR elicit locomotion at low concentration (5 mM). Applications of muscimol (5 mM) or GABA (0.5 M) were found to block chemically-induced locomotion, as well as electrically-elicited and spontaneous walking. Priming infusions of Diazepam amplified the blockage of locomotion by GABA. On the other hand, applications of strychnine (10 mM) were ineffective in inducing stepping, as were infusions of the excitatory agents glutamic acid, acetylcholine and norepinephrine. These findings suggest that the MLR is under inhibitory GABAergic input. The substantia nigra is the only known afferent to the MLR located posterior to the brainstem transection, and is a likely source for this input. A model is proposed to account for our results, as well as those of others, and it provides a working hypothesis for the neurochemical events occurring in brainstem centers which modulate locomotor events.