title: The role of endogenous neurotensin in psychostimulant-induced disruption of prepulse inhibition and locomotion.
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.
authors: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Suite 4000 WMB, 101 Woodruff Circle, Atlanta, GA 30322, USA. rcaceda@med.miami.edu
authors: Ricardo
authors: R
authors: Cáceda
authors: Elisabeth B
authors: EB
authors: Binder
authors: Becky
authors: B
authors: Kinkead
authors: Charles B
authors: CB
authors: Nemeroff
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives; D000661:Amphetamine / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D020233:Gait Disorders, Neurologic / Q000139:chemically induced*; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000009:adverse effects; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D007093:Imidazoles; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C104418:SR 142948A; D009496:Neurotensin; D000661:Amphetamine; D001058:Apomorphine; D000218:Adamantane