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.