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 (10-300nM, 60min) dose-dependently increased (+29+/-3% and +46+/-3% vs basal for the 100 and 300nM concentrations, respectively) local dialysate glutamate levels, while the highest 300nM 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) (10-300nM, 60min) was without effect. Furthermore, the non-peptide neurotensin receptor antagonist SR 48692 (0.2mg/kg) and tetrodotoxin (1microM) fully counteracted the intranigral neurotensin (300nM)-induced increase in local glutamate. SR 48692 (0.2mg/kg) also counteracted the decreases in nigral and ventral thalamic GABA release induced by the peptide. In addition, intranigral perfusion with the dopamine D(2) receptor antagonist raclopride (1microM) fully antagonized the neurotensin (300nM)-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.
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44100, Ferrara, Italy.
L
L
Ferraro
M C
MC
Tomasini
M
M
Fernandez
B W
BW
Bebe
W T
WT
O'Connor
K
K
Fuxe
J C
JC
Glennon
S
S
Tanganelli
T
T
Antonelli
D000818:Animals; D003243:Consciousness / Q000502:physiology; D018492:Dopamine Antagonists; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D020651:Ventral Thalamic Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018492:Dopamine Antagonists; D010446:Peptide Fragments; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin; D018698:Glutamic Acid; D020891:Raclopride; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid