Recovery from unilateral 6-hydroxydopamine lesion of substantia nigra promoted by the neurotachykinin substance P 1-11.

Previous work has indicated that the neurotachykinin substance P may have nootropic and neurotrophic effects in vivo and in vitro raising the possibility that this neuropeptide may promote functional recovery from brain damage. This hypothesis was tested using the unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system, as there is close anatomical and functional interaction between dopamine and substance P in this system. Rats were unilaterally injected with 6-hydroxydopamine into the substantia nigra, and, starting with the day after the lesion, were treated daily with peripheral injections of substance P (50 micrograms/kg, i.p.). The analysis of open-field behavior showed that, compared with vehicle-treated control lesions, substance P prevented the lesion-induced ipsiversive asymmetry in turning behavior and accelerated recovery from the ipsilateral asymmetry in thigmotactic scanning. The facilitatory effects of substance P were dependent on the degree of the lesion, as they were observed in animals with subtotal neostriatal dopamine depletions but not in those with near-total depletions. These results are discussed, firstly, with regard to the possible mechanisms of substance P on dopaminergic and non-dopaminergic systems, and secondly, with respect to their possible relevance in the study of neurodegenerative diseases.