Agmatine disrupts prepulse inhibition of acoustic startle reflex in rats
Date
2010-06
Authors
Uzbay, İsmail Tayfun
Kayır, Hakan
Yıldırım, Murat
Journal Title
Journal ISSN
Volume Title
Publisher
Sage Publications
Abstract
Agmatine is a guanidine-amine formed by the enzymatic decarboxylation of arginine. Agmatine has been proposed to be a neuromodulator and its downstream derivatives, the polyamines, have been suggested to be responsible for sensory gating deficits seen in schizophrenia. In this study, male Wistar rats underwent treatments with agmatine, vehicle or other agents known to alter sensory gating in an experimental paradigm of prepulse inhibition (PPI) of the acoustic startle response. Apomorphine (1 mg/kg s.c.), a nonselective dopamine agonist known to disrupt PPI responses, was injected as the positive reference. Neither apomorphine nor agmatine (40-160 mg/kg i.p.) induced effects on the intensity of startle reflex without a prepulse. However, apomorphine or agmatine (160 mg/kg i.p.) disrupted the PPI of acoustic startle reflex. Furthermore, when given 30 min prior, agmatine acted additively with apomorphine,s effect on PPI. In an attempt to gain more insight, haloperidol (1 and 2 mg/kg i.p.), clozapine (2.5-7.5 mg/kg i.p.) or quetiapine (2.5 and 7.5 mg/kg i.p.) was also injected prior to agmatine (160 mg/kg i.p.). Haloperidol (1 mg/kg) and clozapine (2.5 and 5 mg/kg) were able to prevent the PPI-disrupting effects of apomorphine. However, none of these antipsychotics prevent the PPI-disrupting effects of agmatine. These results suggest that agmatine disrupts the PPI of acoustic startle reflex of rats in a fundamentally different manner than apomorphine does. It may also have a critical role in the pathogenesis of sensorimotor gating-related dysfunctions. © The Author(s), 2010.
Description
Keywords
Acoustic startle reflex, Agmatine, Prepulse inhibition (PPI), Rat(s), Nitric-oxide synthase, Clonidine-displacing substance, Sensorimotor gating deficits, Imidazoline receptors, Schizophrenia, Polyamines, Neurotransmitter, Morphine, Arginine, Blocks, Neurosciences & neurology, Pharmacology & pharmacy, Psychiatry
Citation
Uzbay, İ. T. vd. (2010). "Agmatine disrupts prepulse inhibition of acoustic startle reflex in rats". Journal of Psychopharmacology, 24(6), 923-929.