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

doi:10.1016/S0306-4522(00)00448-6

Neuroscience

Volume 102, Issue 1, 2 January 2001, Pages 113-120

https://doi.org/10.1016/S0306-4522(00)00448-6 Get rights and content

Abstract

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.

Section snippets

Animals

Male adult Sprague–Dawley rats (300–350 g; Stefano Morini, Reggio Emilia, Italy) were kept under regular lighting conditions (12-h/12-h light–dark cycle), and given food and water ad libitum. Following delivery, the animals were allowed to adapt to the environment for at least one week before the experiment started.

Surgery

The animals, kept under halothane anaesthesia (1.5% mixture of halothane and air), were mounted in a David Kopf stereotaxic frame with the upper incisor bar set at −2.5 mm below the

Effects of intranigral neurotensin(1–13) and neurotensin(1–7) on nigral glutamate levels

Basal dialysate SNr glutamate levels in control rats were 0.138±0.019 μM (n=16) and remained constant over the duration of the experiment (270 min). Intranigral perfusion with NT(1–13) (100 and 300 nM) produced a rapid, prolonged and concentration-dependent increase in nigral glutamate levels. The maximal response at 100 and 300 nM concentration (+29±3% and +46±3% vs basal, respectively) was observed 60 min after the onset of the perfusion with the peptide. The increase induced by NT(1–13) at 100 nM

Discussion

Previous studies indicated that NT exerts a modulatory action on both pre- and postsynaptic elements of the nigrostriatal dopaminergic afferent terminals in the striatum,11., 19., 20., 22., 37. thus suggesting a relevant role for the peptide in modulating the basal ganglia activity. However, little is known about the role of NT in the SNr which, together with the entopeduncular nucleus, represents the main output site of the basal ganglia in the rat, involving in particular the GABAergic

Acknowledgements

This study was supported by Italian CNR (no. 99.02615.CT04) and 60% grants, The Stanley Foundation (USA) and The Health Research Board (Ireland). We thank Professor P. Soubrié (Sanofi-Synthelabo Montpellier, France) for supplying SR 48692.

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

Abstract

Section snippets

Animals

Surgery

Effects of intranigral neurotensin(1–13) and neurotensin(1–7) on nigral glutamate levels

Discussion

Acknowledgements

Trends Neurosci.

Trends Neurosci.

Brain Res. Rev.

Neuroscience

J. biol. Chem.

Neuropharmacology

Eur. J. Pharmac.

Brain Res.

Trends Neurosci.

Neurosci. Lett.

Brain Res.

Peptides

Trends Neurosci.

Prog. Neuropsychopharmac. biol. Psychiat.

Brain Res.

Neuroscience

Brain Res.

Neuroscience

Peptides

Trends pharmac. Sci.

Brain Res.

Brain Res. Rev.

Brain Res.

J. chem. Neuroanat.

Brain Res.

Biochem. biophys. Res. Commun.

Neuroscience

Brain Res.

Neuroscience

Neuroscience

Peptides

Neurosci. Lett.

Neuroscience

Trends pharmac. Sci.