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 e ffects of intranigral perfusion with the tridecapeptide neurotensin on loca l dialysate glutamate and GABA levels in the substantia nigra pars reticula ta and on dialysate GABA levels in the ventral thalamus. Intranigral neurot ensin (10-300 nM, 60 min) dose-dependently increased (+29 +/- 3% and +46 +/ - 3% vs basal for the 100 and 300 nM concentrations, respectively) local di alysate glutamate levels, while the highest 300 nM concentration of the pep tide exerted a long-lasting and prolonged reduction in both local and ventr al thalamic (-20 +/- 4% and -22 +/- 2%, respectively) GABA levels. Intranig ral perfusion with the inactive neurotensin fragment neurotensin(1-7) (10-3 00 nM, 60 min) was without effect. Furthermore, the non-peptide neurotensin receptor antagonist SR 48692 (0.2 mg/kg) and tetrodotoxin (1 muM) fully co unteracted the intranigral neurotensin (300 nM)-induced increase in local g lutamate. SR 48692 (0.2 mg/kg) also counteracted the decreases in nigral an d ventral thalamic GABA release induced by the peptide. In addition, intran igral perfusion with the dopamine D-2 receptor antagonist raclopride (1 muM ) fully antagonized the neurotensin (300 nM)-induced decreases in nigral an d ventral thalamic GABA levels. The ability of nigral neurotensin receptor activation to differently influe nce glutamate and GABA levels, whereby it increases nigral glutamate and de creases both nigral and ventral thalamic GABA levels, suggests the involvem ent of neurotensin receptor in the regulation of basal ganglia output at th e level of the nigra. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.