The neurotensin analog NT69L enhances medial prefrontal cortical dopamine and acetylcholine efflux: Potentiation of risperidone-, but not haloperidol-, induced dopamine efflux

Adam J. Prus*, Mei Huang, Zhu Li, Jin Dai, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

NT69L is a novel neurotensin (8-13) analog that produces atypical antipsychotic-like effects in animal models. Because atypical antipsychotic drugs increase dopamine (DA) and acetylcholine (ACh) efflux in the medial prefrontal cortex and DA efflux in the nucleus accumbens, the present study sought to further evaluate the putative antipsychotic-like effects of NT69L by assessing DA and ACh efflux in these regions. Dual probe microdialysis was conducted in awake freely moving male rats, without using an acetylcholinesterase inhibitor in the perfusion medium. NT69L (1.0 and 3.0 mg/kg) produced significant increases in extracellular DA and ACh efflux in the medial prefrontal cortex. NT69L (1.0 mg/kg, but not 3.0 mg/kg) produced a significant increase of DA, but not ACh, efflux in the nucleus accumbens. Pretreatment with the serotonin (5-HT)1A receptor antagonist WAY100635 (0.2 mg/kg) significantly attenuated the 3.0 mg/kg NT69L-induced increase in medial prefrontal cortical DA efflux. Pretreatment with NT69L (1.0 mg/kg) significantly potentiated the effects of the atypical antipsychotic drug risperidone (0.1 mg/kg) on DA, but not ACh, efflux in the medial prefrontal cortex, while pretreatment with NT69L 1.0 mg/kg failed to alter the effects of haloperidol (0.1 mg/kg) on DA or ACh efflux in either region. These findings further suggest that NT analogs may be useful alone or adjunctively for the treatment of schizophrenia.

Original languageEnglish (US)
Pages (from-to)354-364
Number of pages11
JournalBrain research
Volume1184
Issue number1
DOIs
StatePublished - Dec 12 2007

Keywords

  • Acetylcholine
  • Antipsychotic
  • Dopamine
  • Medial prefrontal cortex
  • Microdialysis
  • NT69L
  • Neurotensin
  • Nucleus accumbens
  • Risperidone
  • Schizophrenia
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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