Ontogeny of l-DOPA-induced locomotion: Expression of c-Fos in the brainstem and basal ganglia of rats

Neonatal rats suspended in harnesses, limbs hanging freely, and injected with 100 mg/kg l-3,4-dihydroxyphenylalanine (l-DOPA), engage in a behavior (air stepping) that closely resembles spontaneous locomotion. Rats no longer demonstrate this response after postnatal day 20 (P20). In the present experiment, an immunohistochemical analysis of the immediate early protein c-Fos was performed as a marker for cellular activity in the brains of suspended rat pups treated with l-DOPA at P15 and P25. Control rats were injected with saline at each age and subjected to the same behavioral protocol. Only P15 rat pups injected with l-DOPA engaged in air stepping and expressed the highest levels of c-Fos reactivity in output nuclei of the basal ganglia, as well as the pedunculopontine (PPN) and cuneiform (Cnf) nuclei. Twenty-five-day-old rats, which did not air step, exhibited reduced c-Fos labeling in these areas as well as in the locus coeruleus (LC). Our findings suggest that excitation of the basal ganglia resulted via afferents from the PPN and/or Cnf, which may develop before reciprocal inhibitory connections are fully mature. We propose that a circumscribed portion of the midbrain, which overlaps with the physiologically defined mesencephalic locomotor region (MLR), is necessary for the production of l-DOPA-induced locomotion. We propose further that this action is induced against a background of heightened arousal during the first three postnatal weeks but comes under inhibitory control in rat pups older than 20 days of age.