Glycine and d-serine, but not d-cycloserine, attenuate prepulse inhibition deficits induced by NMDA receptor antagonist MK-801

Abstract

The findings of the present study suggest that glycine and D: -serine but not D: -cycloserine could attenuate PPI deficits associated with NMDA receptor hypofunction via NMDA glycine sites in the brain.

Effects of low-dose d-serine on recognition and working memory in mice

“…In subchronically MK-801-treated animals, we could no longer observe memory in the object recognition task 4 h after training as we did in normal mice; importantly, D-serine administration reversed this deficit and restored short-term memory of the task. Reversal of the deficits induced by acute MK-801 treatment on recognition memory (Karasawa et al 2008) and prepulse inhibition (Lipina et al 2005;Kanahara et al 2008;Hashimoto et al 2009) by higher doses of D-serine had been previously described. Nevertheless, the long-term effects of chronic NMDA antagonism have a more specific profile of behavioral deficits than acute treatment and are thought to be better models of behavioral and neurochemical alterations in schizophrenia, especially deficits in frontal lobe function (Jentsch and Roth 1999).…”

“…Decreased levels of D-serine have been described in the serum (Hashimoto et al 2003) and cerebrospinal fluid (Bendikov et al 2007;Hashimoto et al 2005) of patients with schizophrenia; moreover, changes in the expression and/or activity of enzymes mediating the synthesis and degradation of D-serine have been shown in postmortem analyses of patients' brains (Steffek et al 2006;Bendikov et al 2007;Madeira et al 2008;Habl et al 2009). Animal studies have also shown that D-serine administration can reverse acute behavioral alterations induced by NMDA blockers such as phencyclidine (PCP) and MK-801, which are frequently used as models for antipsychotic testing Kanahara et al 2008;Nilsson et al 1997).…”

NMDA- and β-Amyloid1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

“…Measurement of D-serine, L-serine, glycine, and glutamate levels in the brain homogenate was performed according to established methods using a column-switching high-performance liquid chromatography (HPLC) system (Shimadzu) (Fukushima et al 2004). A 20 l aliquot sample was processed and analyzed as described previously (Kanahara et al, 2008).…”

Glycine Transporter Inhibitor Attenuates the Psychotomimetic Effects of Ketamine in Healthy Males: Preliminary Evidence

“…The GlyT1 inhibitor, such as (R)- (N-[3-(40-fluorophenyl)-3-(40-phenylphenoxy)propyl]sarcosine (NFPS), has been reported to potentiate NMDAR currents in the presence of glycine (Chen et al, 2003), and NFPS combined with risperidone, but not clozapine, potentiates these currents (Konradsson et al, 2006). Preclinical studies have also demonstrated that a number of Gly-B agonists and GlyT1 inhibitors attenuate a wide range of effects produced by NMDA receptor antagonists PCP, MK-801, and ketamine, including locomotor stimulatory effects, stereotypies, prepulse inhibition deficits, c-fos expression, cortical stimulation, and recognition memory deficits (Contreras, 1990;Gozzi et al, 2008;Hashimoto et al, 2008;Javitt and Frusciante, 1997;Kanahara et al, 2008;Karasawa et al, 2008;Kinney et al, 2003;Nilsson et al, 1997;Tanii et al, 1991Tanii et al, , 1994Toth and Lajtha, 1986). However, this has not yet been demonstrated in humans.…”