Effects of MK-801 and antidepressant drugs in the forced swimming test in rats

J, Maj; Rogóż, Z; Skuza, G; Sowińska, H

doi:10.1016/0924-977x(92)90034-6

Cited by 140 publications

(49 citation statements)

References 12 publications

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“…A possible antidepressant activity of competitive NMDA antagonists was reported (Trullas and Skolnick, 1990;Maj et al, 1992a;Papp and Moryl, 1993), as well as their dopamine-releasing action (We~dzony et al, 1991).…”

Section: Discussionmentioning

confidence: 97%

The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

Rogóż

Skuza

et al. 1996

J. Neural Transmission

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It was found previously that the MK-801 (an uncompetitive NMDA receptor antagonist)-induced locomotor hyperactivity in rats was potently increased by antidepressant drugs. The present paper analysed the locomotor hyperactivity induced by combined treatment with fluoxetine + MK-801 in male Wistar rats. The MK-801 hyperactivity was increased by citalopram (the latter effect was prevented by zacopride and ketanserin), sertraline, p-chloramphetamine, 8-OH-DPAT and TFMPP. The hyperlocomotion caused by fluoxetine + MK-801 was antagonized by tropisetron and zacopride and, to a lesser extent, by ketanserin, ritanserin and NAN-190, but not by WAY 100135, pindolol, metergoline or mianserin. Sulpiride and clozapine were able to inhibit the fluoxetine + MK-801 hyperlocomotion. The hyperlocomotion induced by D-amphetamine or apomorphine was not modified by fluoxetine or citalopram. Fluoxetine increased the release of dopamine (measured by a microdialysis method) in the striatum, induced by MK-801. The obtained results indicate that fluoxetine increases the MK-801-induced locomotor hyperactivity via activation of 5-HT3 receptors and, to a lesser degree, 5-HT2 ones.

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Section: Discussionmentioning

confidence: 97%

The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

Rogóż

Skuza

et al. 1996

J. Neural Transmission

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“…NMDA antagonists such as MK-801, 4,5 ketamine, 6 amantadine 7 and others 8,9 exhibited antidepressant effects in different animal models. Beside the abovementioned report on D-cycloserine, slight antidepressant effects in humans have also been observed with the NMDA receptor antagonists amantadine 10,11 and ketamine.…”

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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“…Support for increased glutamatergic activity in depression comes from magnetic resonance spectroscopy: elevated glutamate levels were found in the occipital cortex of unmedicated subjects with MD [74]. Furthermore, NMDA antagonists such as MK-801 [75,76], ketamine [77], memantine [78], amantadine [79,80] and others [73] have exhibited antidepressant effects in humans. The partial NMDA receptor agonist D -cycloserine demonstrated antidepressant effects at high doses [81].…”

Section: Inflammation Influences the Metabolism Of Serotonin And Noramentioning

confidence: 99%

Immunology of Major Depression

Müller¹

2014

Neuroimmunomodulation

149

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High levels of several proinflammatory components of the immune system, such as interleukin-6, C-reactive protein, tumor necrosis factor (TNF)-α, or neopterin in patients suffering from major depression (MD) point to the involvement of an inflammatory process in the pathophysiology of MD. The direct and indirect effects of cytokines on neurotransmitter storage and release - mediated by microglia cells and astrocytes - are discussed. The tryptophan/kynurenine metabolism is one of the indirect mechanisms because the enzyme indoleamine 2,3-dioxygenase - a key enzyme of this metabolism in the central nervous system - is driven by pro- and anti-inflammatory cytokines and degrades serotonin. Moreover, neuroactive kynurenines such as kynurenic acid and quinolinic acid act on the glutamatergic neurotransmission as N-methyl-D-aspartate antagonists and agonists, respectively. Alterations of the serotonergic, noradrenergic and glutamatergic neurotransmission have been shown with low-level neuroinflammation and may be involved in symptom generation. Epidemiological and clinical studies show a role for inflammation as a risk factor for MD. A large-scale epidemiological study in MD clearly demonstrates that severe infections and autoimmune disorders are lifetime risk factors for MD. The vulnerability-stress-inflammation model matches with this view as stress may increase proinflammatory cytokines and even contribute to a lasting proinflammatory state. Further support comes from the therapeutic benefit of anti-inflammatory medications such as the cyclo-oxygenase-2 inhibitors, TNF-α antagonists and others, and the anti-inflammatory and immunomodulatory intrinsic effects of antidepressants.

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Effects of MK-801 and antidepressant drugs in the forced swimming test in rats

Cited by 140 publications

References 12 publications

The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

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

Immunology of Major Depression

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