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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-5-25
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1872-7549
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
202
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
192-7
pubmed:meshHeading
pubmed-meshheading:19463701-Acoustic Stimulation, pubmed-meshheading:19463701-Analysis of Variance, pubmed-meshheading:19463701-Animals, pubmed-meshheading:19463701-Antipsychotic Agents, pubmed-meshheading:19463701-Apomorphine, pubmed-meshheading:19463701-Dextroamphetamine, pubmed-meshheading:19463701-Dizocilpine Maleate, pubmed-meshheading:19463701-Dopamine Agonists, pubmed-meshheading:19463701-Dopamine Uptake Inhibitors, pubmed-meshheading:19463701-Excitatory Amino Acid Antagonists, pubmed-meshheading:19463701-Male, pubmed-meshheading:19463701-Neurotensin, pubmed-meshheading:19463701-Peptide Fragments, pubmed-meshheading:19463701-Rats, pubmed-meshheading:19463701-Rats, Sprague-Dawley, pubmed-meshheading:19463701-Schizophrenic Psychology, pubmed-meshheading:19463701-Sensory Gating, pubmed-meshheading:19463701-Startle Reaction, pubmed-meshheading:19463701-Time Factors
pubmed:year
2009
pubmed:articleTitle
The neurotensin agonist NT69L improves sensorimotor gating deficits in rats induced by a glutamatergic antagonist, but not by dopaminergic agonists.
pubmed:affiliation
CNS Therapy Area, Department of Neurobehavior, Roche Pharmaceuticals, Palo Alto, CA 94304, USA.
pubmed:publicationType
Journal Article