Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jan;54(1):79-86.
doi: 10.1016/j.neuropharm.2007.06.004. Epub 2007 Jun 22.

Neurotensin reduces glutamatergic transmission in the dorsolateral striatum via retrograde endocannabinoid signaling

Henry H Yin  1 , Louise Adermark, David M Lovinger
Affiliations

Neurotensin reduces glutamatergic transmission in the dorsolateral striatum via retrograde endocannabinoid signaling

Henry H Yin et al. Neuropharmacology. 2008 Jan.

Abstract

Neurotensin is a peptide that has been suggested to mimic the actions of antipsychotics, but little is known about how it affects synaptic transmission in the striatum, the major input nucleus of the basal ganglia. In this study we measured the effects of neurotensin on EPSCs from medium spiny projection neurons in the sensorimotor striatum, a region implicated in habit formation and control of motor sequences. We found that bath-applied neurotensin reduced glutamate release from presynaptic terminals, and that this effect required retrograde endocannabinoid signaling, as it was prevented by the CB1 cannabinoid receptor antagonist AM251. Neurotensin-mediated inhibition of striatal EPSCs was also blocked by antagonists of D2-like dopamine receptors and group I metabotropic glutamate receptors, as well as by intracellular calcium chelation and phospholipase C inhibition. These results suggest that neurotensin can indirectly engage an endocannabinoid-mediated negative feedback signal to control glutamatergic input to the basal ganglia.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Bath application of NT reduced amplitude of EPSCs recorded from MSNs in the dorsolateral striatum. A) NT did not affect EPSC amplitude when the stimulating electrode was placed in the white matter just above the dorsolateral striatum, but a significant inhibition was observed after NT application when the stimulating electrode was placed in the striatum. B) A replication of the results using intrastriatal stimulation with different doses of NT, showing the amplitude of the first EPSC for each group.
Figure 2
Figure 2
A) The results using intrastriatal stimulation with 0.5 µM NT, the most effective dose in inhibiting striatal EPSCs, showing the changes in the first and second of the paired EPSCs. The two pulses were 50 ms apart, and given every 20 s. Note the relatively larger inhibition of the first EPSC of the pair. B) In the presence of the NTS1 antagonist SR 142948, NT failed to alter EPSC amplitude or PPR.
Figure 3
Figure 3
NT-induced inhibition of EPSCs in the dorsolateral striatum was blocked by the D2 receptor antagonist sulpiride and by group I mGluR antagonists. A) Experiment performed in the presence of sulpiride, showing that NT failed to reduce EPSC amplitude. B) Experiment performed with sulpiride applied after NT application, showing that sulpiride applied after the onset of inhibition failed to reverse it. C) Experiment performed in the presence of CPCCOEt (mGluR 1 antagonist) and MPEP (mGluR 5 antagonist), showing that NT failed to reduce EPSC amplitude.
Figure 4
Figure 4
NT-induced inhibition of EPSCs in the dorsolateral striatum was blocked and reversed by CB1 receptor antagonism. A) Experiment performed in the continuous present of the CB1 antagonist AM251, NT failed to reduce EPSC amplitude. B) Experiment in which AM251 was applied just after the end of the NT application, showing that the NT-induced inhibition of EPSCs was reversed by bath application of AM251.
Figure 5
Figure 5
NT-induced inhibition of EPSCs in the dorsolateral striatum requires a rise in intracellular calcium and the activation of the PLC pathway. A) When the fast calcium chelator BAPTA was loaded into the postsynaptic cell via the patch pipette, no inhibition of EPSCs was observed after NT application. B) When the PLC inhibitor U73122 was loaded into the postsynaptic cell via the patch pipette, no inhibition of EPSCs was observed after NT application.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Battaini F, Govoni S, Di Giovine S, Trabucchi M. Neurotensin effect on dopamine release and calcium transport in rat striatum: interactions with diphenylalkylamine calcium antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1986;332:267–270. - PubMed
    1. Belmeguenai A, Desrues L, Leprince J, Vaudry H, Tonon MC, Louiset E. Neurotensin stimulates both calcium mobilization from inositol trisphosphate-sensitive intracellular stores and calcium influx through membrane channels in frog pituitary melanotrophs. Endocrinology. 2003;144:5556–5567. - PubMed
    1. Boudin H, Pelaprat D, Rostene W, Beaudet A. Cellular distribution of neurotensin receptors in rat brain: immunohistochemical study using an antipeptide antibody against the cloned high affinity receptor. J Comp Neurol. 1996;373:76–89. - PubMed
    1. Caceda R, Kinkead B, Nemeroff CB. Neurotensin: role in psychiatric and neurological diseases. Peptides. 2006;27:2385–2404. - PubMed
    1. Calabresi P, Maj R, Pisani A, Mercuri NB, Bernardi G. Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci. 1992;12:4224–4233. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources