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Agmatine attenuates the disruptive effects of phencyclidine on prepulse inhibition.

Journal article
Authors Erik Pålsson
Kim Fejgin
Caroline Wass
Daniel Klamer
Published in European journal of pharmacology
Volume 590
Issue 1-3
Pages 212-6
ISSN 0014-2999
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 212-6
Language en
Links dx.doi.org/10.1016/j.ejphar.2008.06...
Keywords Agmatine, pharmacology, Animals, Dose-Response Relationship, Drug, Male, Mental Processes, drug effects, Mice, Nitric Oxide Synthase, antagonists & inhibitors, Phencyclidine, pharmacology, Receptors, N-Methyl-D-Aspartate, antagonists & inhibitors, Startle Reaction, drug effects
Subject categories Pharmacology and Toxicology

Abstract

Agmatine, a decarboxylation product of arginine, is thought to be an important neuromodulator in the mammalian brain. It is proposed to exert neuroprotective, anxiolytic and antidepressant effects. The receptor-binding profile of agmatine is complex and includes interaction with alpha(2)-adrenergic and imidazoline I(1) receptors. Furthermore, agmatine is an NMDA-receptor antagonist and inhibits nitric oxide synthase. Prepulse inhibition (PPI) of the acoustic startle response is used as a measure of the pre-attentive information processing. PPI is lowered in schizophrenia and this impairment can be mimicked in experimental animals using the psychotomimetic drug phencyclidine (PCP). The aim of the present study was to investigate the effects of agmatine per se on the PPI response and the effects of agmatine pre-treatment on a PCP-induced disruption of PPI. Agmatine administration (10, 20 and 40 mg/kg) did not change the PPI response or the acoustic startle response. However, pre-treatment with agmatine 20 mg/kg, but not agmatine 40 mg/kg, significantly attenuated a PCP (5 mg/kg)-induced disruption of the PPI response. These results emphasize the potential role of agmatine as a neuromodulator and potential target for novel treatments for brain disorders.

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