Functional neuroanatomy of the nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat—I. Effects of perfusion with tetrodotoxin and low-calcium medium

Abstract

In the present study we employed the dual probe approach to investigate functional interactions between the nigrostriatal dopaminergic and striatonigral GABAergic pathways in the awake, freely moving rat and their role in motor function. One microdialysis probe of concentric design was implanted in the substantia nigra pars reticulata and another in the ipsilateral dorsolateral striatum. Perfusion with a low-Ca2+ (0.1 mM) medium and with the voltage-dependent Na(+)-channel blocker tetrodotoxin (10 microM) was alternatively performed in both brain regions and the dialysate dopamine, glutamate and GABA levels were simultaneously measured in the dorsolateral striatum, whereas GABA levels alone were monitored in the substantia nigra. Perfusion with a low-Ca2+ medium in the substantia nigra pars reticulata did not affect local GABA levels, but transiently increased striatal dopamine release (+40%) without modifying striatal glutamate and GABA levels. Conversely, intranigral perfusion with tetrodotoxin transiently increased local GABA levels (+40%), while it decreased striatal dopamine (-60%) and increased glutamate (+70%) and GABA (+50%) levels. Perfusion with a low-Ca2+ medium in the dorsolateral striatum reversibly decreased local dopamine (-70%), glutamate (-20%) and GABA (-20%) levels, while local perfusion with tetrodotoxin decreased dopamine (-70%), increased glutamate (+30%) but did not affect dialysate GABA levels in this brain area. Neither of these intrastriatal treatments significantly affected GABA levels in the substantia nigra. Intranigral but not intrastriatal perfusion with tetrodotoxin was also associated with an increase in spontaneous locomotor activity as expressed by contralateral turning. Intranigral and intrastriatal perfusion with low-Ca2+ medium did not influence locomotor activity. On the basis of these neurochemical and behavioural findings, we propose a new dynamic model for the study of motor behaviour as mediated by basal ganglia circuitry.