Dizocilpine (MK-801) increases not only dopamine but also serotonin and norepinephrine transmissions in the nucleus accumbens as measured by microdialysis in freely moving rats

Yan, Qing‐Shan; Reith, Maarten E. A.; Jobe, Phillip C.; Dailey, John W.

doi:10.1016/s0006-8993(97)00568-4

Cited by 121 publications

(64 citation statements)

References 66 publications

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Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 74%

“…Doses as low as 0.3 mg/kg have been shown to increase serotonin levels acutely, but the effects of subacute doses are not known (Yan et al 1997). The lack of effect we found with this dose may reflect lower serotonin concentrations that do not result in 5-HT 6 receptor mRNA expression alterations (Yan et al 1997). However, the low micromolar affinity of the dopamine transporter for MK-801 may also help to explain an increase in MK-801-induced serotonin release (Clarke and Reuben 1995).…”

Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 74%

“…However, the low micromolar affinity of the dopamine transporter for MK-801 may also help to explain an increase in MK-801-induced serotonin release (Clarke and Reuben 1995). MK-801 has been shown to increase dopamine, serotonin, and norepinephrine lev- els, and these three neurotransmitters share uptake transporters (Nishimura et al 1998;Yan et al 1997). Therefore, the putative increase in serotonin levels resulting in decreased 5-HT 6 receptor mRNA expression may be attributable to a direct effect on serotonin uptake.…”

Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 99%

“…However, systemic administration of such NMDA receptor antagonists as MK-801 and ketamine also increase serotonin levels, although probably via a mechanism separate from presynaptic NMDA receptors located on raphe neurons (Lindefors et al 1997;Whitton et al 1992;Yan et al 1997). Specifically, these antagonists are postulated to block NMDA receptors on inhibitory GABAergic inputs to the raphe, and this disinhibition is believed to lead to the increased serotonin levels.…”

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confidence: 99%

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Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain

Healy

Meador‐Woodruff

1999

Neuropsychopharmacology

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Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 74%

Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 74%

Section: Experiments 1 Mk-801 Treatment Striatummentioning

confidence: 99%

mentioning

confidence: 99%

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Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain

Healy

Meador‐Woodruff

1999

Neuropsychopharmacology

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“…NMDA receptor antagonists increase the serotonin levels in the brain. 20,21 Several studies showed an increased activity of the glutamatergic system in the peripheral blood of depressive patients, [22][23][24] although this result could not be replicated by all authors. 25 The inconsistency of the findings, however, might be due to medication effects, low statistical power and a lack of appropriate control of diagnosis.…”

Section: Glutamate In Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry

Iravani

Muscat

Kruk

1999

Synapse

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The effects of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) and a competitive NMDA antagonist, (+/-)-3-2-carboxypiperazin-4-yl-propyl-1-phosphonic acid (CPP) were compared in electrically evoked 5-HT release in the brain slices incorporating the substantia nigra pars reticulata (SNr) or the dorsal raphé nucleus (DRN) using fast cyclic voltammetry (FCV). Electrical stimulation of either the SNr or the DRN with 50 pulses at frequencies greater than 10 Hz generated signals that were indistinguishable from 5-HT. In the SNr, 0.6-60 microM MK-801 concentration dependently potentiated stimulated 5-HT release. CPP 20 microM or NMDA 100 microM had no effect on 5-HT release evoked by electrical stimulation. In the SNr, 1 microM fluvoxamine or 0.6-60 microM MK-801 potentiated electrically evoked release of 5-HT. Pre-exposure to 20 microM MK-801 inhibited the enhancing effects of 1 microM fluvoxamine on electrically evoked 5-HT release in the SNr. In the DRN, the presence of 1 microM fluvoxamine or 20 microM MK-801 weakly potentiated 5-HT release. In the presence of 1 microM methiothepin (a nonselective 5-HT1-2 antagonist), 1 microM fluvoxamine or 20 microM MK-801 were equipotent in potentiating the concentration of 5-HT released in response to electrical stimulation. The T1/2 values for 5-HT release following MK-801 or fluvoxamine administration were significantly increased. Potentiation of 5-HT release by MK-801 in the SNr and the DRN and lack of effect of either CPP or NMDA on 5-HT release or uptake argues against a role for NMDA receptors in modulation of 5-HT release. Inhibition of fluvoxamine induced potentiation of 5-HT signal in the presence of MK-801 suggests that MK-801 and fluvoxamine may interact at the level of the 5-HT transporter.

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Dizocilpine (MK-801) increases not only dopamine but also serotonin and norepinephrine transmissions in the nucleus accumbens as measured by microdialysis in freely moving rats

Cited by 121 publications

References 66 publications

Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain

Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry

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