The role of endogenous neurotensin in psychostimulant-induced disruption of prepulse inhibition and locomotion

Ricardo Cáceda, Elisabeth B. Binder, Becky Kinkead, Charles B. Nemeroff

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The neuropeptide neurotensin (NT) is closely associated with dopaminergic and glutamatergic systems in the rat brain. Central injection of NT into the nucleus accumbens (NAcc) or peripheral administration of NT receptor agonists, reduces many of the behavioral effects of psychostimulants. However, the role of endogenous NT in the behavioral effects of psychostimulants (e.g. DA agonists and NMDA receptor antagonists) remains unclear. Using a NTR antagonist, SR142948A, the current studies were designed to examine the role of endogenous NT in DA receptor agonist- and NMDA receptor antagonist-induced disruption of prepulse inhibition of the acoustic startle response (PPI), locomotor hyperactivity and brain-region specific . c-fos mRNA expression. Adult male rats received a single i.p. injection of SR142948A or vehicle followed by . d-amphetamine, apomorphine or dizocilpine challenge. SR142948A had no effect on baseline PPI, but dose-dependently attenuated . d-amphetamine- and dizocilpine-induced PPI disruption and enhanced apomorphine-induced PPI disruption. SR142948A did not significantly affect either baseline locomotor activity or stimulant-induced hyperlocomotion. Systemic SR142948A administration prevented . c-fos mRNA induction in mesolimbic terminal fields (prefrontal cortex, lateral septum, NAcc, ventral subiculum) induced by all three psychostimulants implicating the VTA as the site for NT modulation of stimulant-induced PPI disruption. Further characterization of the NT system may be valuable to find clinical useful compounds for schizophrenia and drug addiction.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalSchizophrenia Research
Volume136
Issue number1-3
DOIs
StatePublished - Apr 1 2012

Keywords

  • Apomorphine
  • C-fos
  • D-amphetamine
  • Dizocilpine
  • Locomotion
  • Neurotensin
  • Prepulse inhibition

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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