Research article summary (published 30 Mar 2009):

The neurotensin agonist NT69L improves sensorimotor gating deficits in rats induced by a glutamatergic antagonist, but not by dopaminergic agonists.

Full Abstract

An imbalance between different neurotransmitter systems is involved in the pathophysiological processes underlying schizophrenia. Since the neurotensin (NT) system modulates the activity of several of these neurotransmitters, drugs acting upon the NT system may act as novel antipsychotic drugs. This hypothesis is supported by studies with NT in animal models. For example, intracranial injection of NT improves sensorimotor gating in rats [Feifel D, Minor KL, Dulawa S, Swerdlow NR. The effects of intra-accumbens neurotensin on sensorimotor gating. Brain Research 1997;760:80-4]. NT-mimetics, such as NT69L, have been developed which are more resistant to enzymatic degradation than the native NT peptide. In the present study, the potential antipsychotic properties of NT69L were evaluated in a rat pre-pulse inhibition (PPI) paradigm. PPI is a measure of sensorimotor gating where a weak auditory stimulus, or pre-pulse, inhibits the startle response to a strong stimulus, or pulse. Schizophrenic patients exhibit deficits in their PPI response. This condition can be mimicked in rats with psychotomimetic drugs and the resulting PPI deficit is reversed by antipsychotic drugs. NT69L (0.1-10mg/kg i.p.) reversed disruptions of the PPI response induced by the NMDA antagonist dizocilpine (0.1mg/kg s.c.) for at least 1-h post-injection, but did not reverse disruptions induced by the dopaminergic agonists apomorphine and d-amphetamine (0.5 and 5mg/kg s.c., respectively). These results confirm that NT69L possesses antipsychotic-like activity and therefore could be beneficial in the treatment of schizophrenia.

Author information

Author/s: Secchi, R L (RL); Sung, E (E); Hedley, L R (LR); Button, D (D); Schreiber, R (R);

Affiliation: CNS Therapy Area, Department of Neurobehavior, Roche Pharmaceuticals, Palo Alto, CA 94304, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Behavioural brain research (Behav Brain Res), published in Netherlands. (Language: eng)

Reference: 2009-Sep; vol 202 (issue 2) : pp 192-7

Dates: Created 2009/05/25; Completed 2009/08/19;

PMID: 19463701, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acoustic Stimulation Analysis of Variance Animals Antipsychotic Agents - administration & dosage Apomorphine - administration & dosage Dextroamphetamine - administration & dosage Dizocilpine Maleate - administration & dosage Dopamine Agonists - administration & dosage Dopamine Uptake Inhibitors - administration & dosage Excitatory Amino Acid Antagonists - administration & dosage

Excitatory Amino Acid Antagonists - administration & dosage Male Neurotensin - administration & dosage; analogs & derivatives Peptide Fragments - administration & dosage Rats Rats, Sprague-Dawley Schizophrenic Psychology Sensory Gating - drug effects Startle Reaction - drug effects Time Factors

Associated Chemicals: Antipsychotic Agents (0) ; Dopamine Agonists (0) ; Dopamine Uptake Inhibitors (0) ; Excitatory Amino Acid Antagonists (0) ; Peptide Fragments (0) ; neurotensin 69L (0) ; Neurotensin (39379-15-2) ; Dextroamphetamine (51-64-9) ; Apomorphine (58-00-4) ; Dizocilpine Maleate (77086-22-7)

Related articles

These are the highest related articles currently in the database:

• The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice. 30 Mar 2004
• Effects of nicotine on quinpirole- and dizocilpine (MK-801)-induced sensorimotor gating impairments in rats. 7 Jul 2008
• Novel antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist. 30 Jan 1999
• Effects of repeated injections of the neurotensin analog NT69L on dopamine release and uptake in rat striatum in vitro. 27 Oct 2004
• Does sensitization occur to prepulse inhibition of the startle reflex effects of repeated apomorphine treatments in rats? 30 Dec 1998
• Effects of acute or chronic administration of risperidone on motor and sexual behavior of male rats. 30 Dec 1996
• Effects of 5 daily injections of the neurotensin-mimetic NT69L on the expression of neurotensin receptors in rat brain. 27 Jul 2005
• SCH 23390 in the prefrontal cortex enhances the effect of apomorphine on prepulse inhibition of rats. 3 Jun 2006
• Apomorphine, d-amphetamine, strychnine and yohimbine do not alter prepulse inhibition of the acoustic startle reflex. 30 Dec 1987
• Apomorphine effects on emotional modulation of the startle reflex in rats. 13 Oct 2005

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.