RGD Reference Report - Neurotensin activates GABAergic interneurons in the prefrontal cortex. - Rat Genome Database

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Neurotensin activates GABAergic interneurons in the prefrontal cortex.

Authors: Petrie, KA  Schmidt, D  Bubser, M  Fadel, J  Carraway, RE  Deutch, AY 
Citation: Petrie KA, etal., J Neurosci. 2005 Feb 16;25(7):1629-36.
RGD ID: 9743972
Pubmed: PMID:15716398   (View Abstract at PubMed)
PMCID: PMC6725935   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3579-04.2005   (Journal Full-text)

Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administration of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]t ricyclo(3.3.1.1 [EC] .3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. We found that D2 agonist-elicited increases in PFC GABA levels were blocked by pretreatment with SR48692, consistent with data indicating that D2 autoreceptor agonists increase neurotensin release from dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin plays an important role in regulating prefrontal cortical interneurons and that it may be useful to consider neurotensin agonists as an adjunct in the treatment of schizophrenia.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of gamma-aminobutyric acid secretion  IMP 9743972 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntsr1  (neurotensin receptor 1)


Additional Information