| The globus pallidus is an important structure in the indirect pathway of basal ganglia circuit. By innervating all the basal ganglia nuclei, the globus pallidus plays a critical role in movement regulation. Neurotensin is a tridecapeptide which plays an important role in the central nervous system by acting either as a neurotransmitter or a neuromodulator. Previous studies have shown that neurotensin plays a role in the pathophysiology of several central nervous system disorders. Systemic administration of a neurotensin analog that can cross the blood-brain barrier produced antiparkinson-like effects in 6-hydroxydopamine-lesioned rats. Morphological studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and both neurotensin type-1 and type-2 receptors are present in the globus pallidus. Object: To study the effects of neurotensin on the firing properties of globus pallidus neurons in normal and parkinsonian rats, and behavioral effects of neurotensin in awake rats. Methods: In vivo extracellular single unit recordings and cannulae embedded technique were used in the present study. Results: 1. Micro-pressure ejection of neurotensin into the globus pallidus increased spontaneous firing rate of pallidal neurons. In 24 out of 49 globus pallidus neurons, 0.1 mM neurotensin increased the firing rate from 10.28±1.48 Hz to 14.86±2.01 Hz (P＜0.001). The average increase was 47.41±4.43%. Within the range of concentration from 0.001 mM to 1 mM, neurotensin produced a clear bell-shaped concentration-dependent effects in increasing the firing rate of globus pallidus neurons. After lesioning pallidal cholinergic neurons, 0.1 mM neurotensin still increased the firing rate in 9 out of 24 globus pallidus neurons. The average increase was 36.67±7.29%, which was not statistically different compared to that without 192 IgG-saporin treatment (P＞0.05). 2. The excitatory effects of neurotensin could be mimicked by the C-terminal fragment, neurotensin (8-13), which increased the firing rate by 60.32±8.96% (P＜0.001) at 3 mM, but not by the N-terminal fragment, neurotensin (1-8). 3. Local administration of both a non-selective neurotensin receptor antagonist, SR142948A, and the selective neurotensin type-1 receptor antagonist, SR48692, blocked the excitatory effects induced by neurotensin. 4. In 6-hydroxydopamine lesioned rats, 0.1 mM neurotensin increased the firing rate in 8 out of 20 globus pallidus neurons on the lesioned side. The average increase was 38.09±5.32%. On the unlesioned side, 0.1 mM neurotensin increased the firing rate in 10 out of 17 globus pallidus neurons. The average increase was 85.88±18.91%, which was significantly stronger compared with that on the lesioned side (P＜0.05). 5. In the behaving rats, we further observed the postural effects of neurotensin in the globus pallidus. Unilateral microinjection of neurotensin into the globus pallidus induced a SR48692 sensitive contralateral dystonic posturing in the presence of systemic haloperidol administration, which could be accounted for by the electrophysiological effects of neurotensin in increasing the firing rate of pallidal neurons. Conclusion: Our in vivo electrophysiological and behavioral results suggest that neurotensin increases the activity of globus pallidus neurons via neurotensin type-1 receptors. The present findings provide a rationale for further investigations into its potential in the treatment of motor disorders originating from the basal ganglia. |
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