Glycine and D-serine decrease MK-801-induced hyperactivity in mice

Nilsson, Mikael; Carlsson, Arvid; Carlsson, Maria

doi:10.1007/bf01294720

Cited by 52 publications

(33 citation statements)

References 31 publications

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“…Hence, development of NMDA receptor antagonists for therapeutic use in PD has been pursued actively during the past few years. But these glutamate antagonists have very low effectiveness, and a plethora of side effects that have limited their clinical utility as neuroprotectants (Sonsalla et al, 1992;Engber et al, 1994;Nilsson et al, 1997;Li et al, 2002). An alternate strategy is to attenuate the excitotoxic response in the basal ganglia by indirectly modulating other interacting neurotransmitter systems.…”

Section: Discussionmentioning

confidence: 99%

“…Glutamate binds to a variety of excitatory amino acid receptors, especially the NMDA receptor, leading to prolonged and excessive depolarization and neuronal activation resulting in the death of target neurons (Choi, 1988;Lynch and Dawson, 1994). Consequently, NMDA receptor blockade in PD research has been actively pursued over the past decade, but to date has been limited by the side effects of the glutamate antagonists (Nilsson et al, 1997;Li et al, 2002) and their mixed effectiveness (Sonsalla et al, 1992;Engber et al, 1994).…”

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confidence: 99%

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5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

Madhavan

Freed

Anantharam

et al. 2002

J Pharmacol Exp Ther

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Apoptosis and glutamate-mediated excitotoxicity may play a role in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). In the present study, we investigated whether stimulation of the 5-hydroxytryptamine 1A (5-HT1A) receptor attenuates N-methyl-D-aspartate-(NMDA) and 1-methyl-4-phenylpyridinium (MPP ϩ )-induced apoptotic cell death in cell culture models. A brief exposure (20 min) of M213-2O striatal cells to NMDA and glutamate produced a delayed increase in caspase-3 activity and DNA fragmentation in a dose-and time-dependent manner. NMDA-induced caspase-3 activity and DNA fragmentation were almost completely blocked by the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and (R)-5-fluoro-8 hydroxy-2-(dipropylamino)-tetralin (R-UH-301). Additionally, the protective effects of 8-OH-DPAT and R-UH-301 on NMDA-induced caspase-3 activation and apoptosis were reversed by pretreatment with the 5-HT1A antagonists N- [2-[4-(2-methoxyphenyl(WAY 100635) and S-UH-301, respectively. Similarly, doseand time-dependent increases in caspase-3 activity and DNA fragmentation were observed in rat primary mesencephalic neurons after a brief exposure to NMDA and glutamate. Caspase-3 activation and DNA fragmentation in primary mesencephalic neurons were almost completely inhibited by 8-OH-DPAT. This neuroprotective effect of 8-OH-DPAT was reversed by WAY 100635. Additionally, 8-OH-DPAT blocked tyrosine hydroxylase (TH)-positive cell death after NMDA exposure and also almost completely attenuated the NMDA-induced Ca 2ϩ influx in primary mesencephalic cultures. Furthermore, 8-OH-DPAT and R-UH-301 blocked apoptotic cell death in the primary mesencephalic neurons that were exposed to the Parkinsonian toxin MPP ϩ . Together, these results suggest that 5-HT1A receptor stimulation may be a promising pharmacological approach in the development of neuroprotective agents for PD.Parkinson's disease (PD) is a major neurodegenerative disorder with a lifetime incidence of 1 to 2%. The drug L-DOPA has been the gold standard PD treatment for more than three decades now and can bring considerable relief from the debilitating symptoms of the disease. However, its long-term use has several limitations, including severe fluctuations in effectiveness and drug-induced involuntary movements (Fahn, 1999;Carlsson, 2002). Importantly, L-DOPA simply compensates for the dopamine deficiency in Parkinson's patients and fails to attenuate the progression of the disease. Hence, novel neuroprotective agents designed to interfere with the basic pathogenic mechanism of cell death in PD are clearly needed.Excitotoxic mechanisms may contribute to the nigrostriatal degeneration in PD (Greenamyre, 1993;Olanow and Tatton, 1999). Glutamate binds to a variety of excitatory amino acid receptors, especially the NMDA receptor, leading to prolonged and excessive depolarization and neuronal activation resulting in the death of target neurons (Choi, 1988;

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

Madhavan

Freed

Anantharam

et al. 2002

J Pharmacol Exp Ther

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“…Both glycine Toth and Lajtha, 1986) and D-serine (Contreras, 1990;Nilsson et al, 1997) have been shown to reverse the behavioral effects of PCP in rodents following acute administration, indicating the in vivo relevance of the interaction. The effects of these agents during long-term administration, however, have not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Reversal of Phencyclidine-Induced Dopaminergic Dysregulation by N-Methyl-D-Aspartate Receptor/Glycine-site Agonists

Javitt

Balla

Burch

et al. 2003

Neuropsychopharmacol

101

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N-methyl-D-aspartate (NMDA) receptors may play a critical role in the pathophysiology of schizophrenia. In rodents, NMDA receptor antagonists, such as phencyclidine (PCP), induce dopaminergic dysregulation that resembles the pattern observed in schizophrenia. The present study investigates the degree to which concurrent treatment with NMDA modulators, such as glycine and the recently developed glycine transport antagonist N[3-(4 00 -fluorophenyl)-3-(4 00 -phenylphenoxy)propyl]sarcosine (NFPS) prevents dopaminergic dysregulation observed following chronic (3 months) or subchronic (2 weeks) PCP administration. Both chronic and subchronic treatment with PCP in the absence of glycine or NFPS led to significant potentiation of amphetamine-induced dopamine release in the prefrontal cortex and striatum, similar to that observed in schizophrenia. Treatment with either high-dose glycine or NFPS along with PCP prevented PCP effects. These findings demonstrate effective doses of glycine for use in animal models of schizophrenia, and support recent clinical studies showing the effectiveness of NMDA agonists in the treatment of persistent symptoms of schizophrenia.

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“…Therefore, NMDA receptor antagonist-treated animals have been widely used as models of schizophrenia (Noda et al, 1995;Sams-Dodd, 1996;Nilsson et al, 1997;Enomoto et al, 2005Enomoto et al, , 2007. To evaluate the effects of TAK-063 on spatial working memory deficits produced by an NMDA receptor antagonist, the Y-maze test and radial arm maze task were used (Lalonde, 2002;Hughes, 2004;AbdulMonim et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models

Shiraishi

Suzuki

Harada

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Cognitive deficits in various domains, including recognition memory, attention, impulsivity, working memory, and executive function, substantially affect functional outcomes in patients with schizophrenia. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl) phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4 (1H)-one] is a potent and selective phosphodiesterase 10A inhibitor that produces antipsychotic-like effects in rodent models of schizophrenia. We evaluated the effects of TAK-063 on multiple cognitive functions associated with schizophrenia using naïve and drug-perturbed rodents. TAK-063 at 0.1 and 0.3 mg/kg p.o. improved time-dependent memory decay in object recognition in naïve rats. TAK-063 at 0.1 and 0.3 mg/kg p.o. increased accuracy rate, and TAK-063 at 0.3 mg/kg p.o. reduced impulsivity in a five-choice serial reaction time task in naïve rats. N-methyl-D-aspartate receptor antagonists, such as phencyclidine and MK-801 [(5R,10S)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine], were used to induce working memory deficits relevant to schizophrenia in animals. TAK-063 at 0.3 mg/kg p.o. attenuated both phencyclidine-induced working memory deficits in a Y-maze test in mice and MK-801-induced working memory deficits in an eight-arm radial maze task in rats. An attentional set-shifting task using subchronic phencyclidine-treated rats was used to assess the executive function. TAK-063 at 0.3 mg/kg p.o. reversed cognitive deficits in extradimensional shifts. These findings suggest that TAK-063 has a potential to ameliorate deficits in multiple cognitive domains impaired in schizophrenia.

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Glycine and D-serine decrease MK-801-induced hyperactivity in mice

Cited by 52 publications

References 31 publications

5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

Reversal of Phencyclidine-Induced Dopaminergic Dysregulation by N-Methyl-D-Aspartate Receptor/Glycine-site Agonists

The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models

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