The novel neurotensin analog NT69L blocks phencyclidine (PCP)-induced increases in locomotor activity and PCP-induced increases in monoamine and amino acids levels in the medial prefrontal cortex.

Brain Research
Zhimin LiElliott Richelson

Abstract

Schizophrenia is a life-long, severe, and disabling brain disorder that requires chronic pharmacotherapy. Because current antipsychotic drugs do not provide optimal therapy, we have been developing novel treatments that focus on receptors for the neuropeptide neurotensin (NT). NT69L, an analog of neurotensin(8-13), acts like an atypical antipsychotic drug in several dopamine-based animal models used to study schizophrenia. Another current animal model utilizes non-competitive antagonists of the NMDA/glutamate receptor, such as the psychotomimetic phencyclidine (PCP). In the present study, we investigated the effects of NT69L on PCP-induced behavioral and biochemical changes in the rat. The top of an activity chamber was modified to allow us to perform microdialysis in rat brain, while simultaneously recording the locomotor activity of a rat. PCP injection significantly increased activity as well as the extracellular concentration of norepinephrine (NE), 5-HT, dopamine (DA), and glutamate in the medial prefrontal cortex (mPFC). Pretreating with NT69L blocked the PCP-induced hyperactivity as well as the increase of DA, 5-HT, NE, and glutamate in mPFC. Interestingly and unexpectedly, NT69L markedly increased glycine levels, while ...Continue Reading

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Citations

Aug 15, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hendrik WesselingSabine Bahn
Jan 15, 2011·The Journal of Biological Chemistry·Dominic ThibaultLouis-Éric Trudeau
Jan 13, 2011·Neurobiology of Learning and Memory·Tanya J WilliamsTeresa A Milner
Oct 27, 2010·Neuroscience Letters·Zhimin LiElliott Richelson
Mar 29, 2014·Drug Testing and Analysis·Hamilton Morris, Jason Wallach
Aug 19, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shivali KohliKevin C F Fone

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