L-DOPA-INDUCED AIR-STEPPING IN DECEREBRATE DEVELOPING RATS

Developing rats were anesthetized and a precollicular brainstem transection performed. Administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg, s.c.) induced locomotion in groups of animals 0-3, 6-8, 14-16 and 20-22 days of age. At early stages in development (0-3 days), continuous, long-lasting air-stepping was induced consisting of 4-limb walking with stronger alternation in the forelimbs compared to the hindlimbs. At 6-8 days of age, continuous air-stepping was characterized by better agreement between forelimb and hindlimb step cycles. By 14-16 days of age, the hindlimbs showed stronger and faster stepping than the forelimbs. The first evidence of consistent galloping was observed in this age group. In some cases, the forelimbs were held extended and only the hindlimbs walked or galloped. At 20-22 days, walking and galloping became episodic and the hindlimbs typically galloped while the forelimbs alternated. Each age group was tested for overground locomotion. Only in the 20-22 day group was weight-bearing overground stepping observed. At earlier ages, limb alternation was evident but of insufficient strength to lift the body off the ground. In general, the duration of the effect of the same dose of L-DOPA decreased with age. Animals in each group which received a mid-thoracic spinal cord transection showed forelimb alternation but no hindlimb stepping. These results indicate that L-DOPA induces stepping by activating brainstem and/or spinal centers via an as yet unknown mechanism. The pattern of the development of gait (forelimb to hindlimb gradient) at various ages was similar to that observed in intact developing rats.