Evidence that nigral substance P controls the activity of the nigrotectal GABAergic pathway.

The unilateral intranigral application of either of two substance P (SP) analogs with antagonist properties ( [DPro2,D-Phe7,D-Trp9]-SP and [D-Pro2,D-Trp7,9]-SP) induced a significant (37%) decrease in GABA turnover in the target region of the nigrotectal projections, namely the deep layers of the superior colliculus in the homolateral hemisphere, and was without any effect in the superficial layers. This action was not prevented by coinjection of the GABA antagonist bicuculline-methiodide. There was no effect of these SP analogs on GABA turnover in the deep layers of superior colliculus when they were microinjected in the ipsilateral median forebrain bundle or in the contralateral substantia nigra. These results are consistent with the proposal that nigral SP exerts a tonic excitatory action on efferent GABAergic projections from pars reticulata of substantia nigra.