Nigral neurotensin receptor regulation of nigral glutamate and nigroventral thalamic GABA transmission: A dual-probe microdialysis study in intact conscious rat brain

Dual-probe microdialysis in the awake rat was employed to investigate the effects of intranigral perfusion with the tridecapeptide neurotensin on local dialysate glutamate and GABA levels in the substantia nigra pars reticulata and on dialysate GABA levels in the ventral thalamus. Intranigral neurotensin (10-300 nM, 60 min) dose-dependently increased (+29 ± 3% and +46 ± 3% vs basal for the 100 and 300 nM concentrations, respectively) local dialysate glutamate levels, while the highest 300 nM concentration of the peptide exerted a long-lasting and prolonged reduction in both local and ventral thalamic (-20 ± 4% and -22 ± 2%, respectively) GABA levels. Intranigral perfusion with the inactive neurotensin fragment neurotensin(1-7) (10-300 nM, 60 min) was without effect. Furthermore, the non-peptide neurotensin receptor antagonist SR 48692 (0.2 mg/kg) and tetrodotoxin (1 μM) fully counteracted the intranigral neurotensin (300 nM)-induced increase in local glutamate. SR 48692 (0.2 mg/kg) also counteracted the decreases in nigral and ventral thalamic GABA release induced by the peptide. In addition, intranigral perfusion with the dopamine D₂ receptor antagonist raclopride (1 μM) fully antagonized the neurotensin (300 nM)-induced decreases in nigral and ventral thalamic GABA levels. The ability of nigral neurotensin receptor activation to differently influence glutamate and GABA levels, whereby it increases nigral glutamate and decreases both nigral and ventral thalamic GABA levels, suggests the involvement of neurotensin receptor in the regulation of basal ganglia output at the level of the nigra.