The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801

Bubeníková-Valešová, Věra; Votava, Martin; Páleníček, Tomáš; Horáček, Jiří

doi:10.1016/j.neuropharm.2006.11.004

Cited by 21 publications

(21 citation statements)

References 34 publications

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“…The treatment regimen with MK-801 was based on our previous report (Bubenikova-Valesova et al 2007b). The N-methyl-D-aspartate receptor antagonist MK-801 (Sigma-Aldrich, Czech Republic; Dizocilpine maleate; [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine), at a dose of 0.1 mg/kg, was dissolved in saline.…”

Section: Drugsmentioning

confidence: 99%

“…Locomotor activity in a novel environment Locomotor activity, expressed as total distance travelled during 30 min in a box (68×68×30 cm) located in a soundproof room, was measured using a video tracking system for automation of the behavioural experiments (Noldus, Netherlands, EthoVision Colour Pro-Version 3.1), as described previously (Bubenikova-Valesova et al 2007b). …”

Section: Apparatus and Behavioural Proceduresmentioning

confidence: 99%

“…Anxiolytic properties of tandospirone, as marketed in Japan, have been demonstrated in human and animal studies (Nishikawa et al 2007;Nishitsuji et al 2004;Nishitsuji et al 2006;Sugimoto et al 1998). Furthermore, Sumiyoshi and colleagues (Bubenikova-Valesova et al 2007b;Sumiyoshi et al 2000;Sumiyoshi et al 2001b;Sumiyoshi et al 2001a;Sumiyoshi et al 2007a) conducted a series of studies on the effect of the addition of tandospirone to ongoing treatment with small to moderate doses of antipsychotic drugs on cognitive function in patients with schizophrenia. Specifically, they found that the addition of tandospirone (30 mg/day) to the typical antipsychotic drug regime for 4-6 weeks improved cognitive function in patients with schizophrenia (BubenikovaValesova et al 2007b;Sumiyoshi et al 2000;Sumiyoshi et al 2001b;Sumiyoshi et al 2001a;Sumiyoshi et al 2007a).…”

Section: Introductionmentioning

confidence: 99%

“…The principal purpose of this study was to test the hypothesis that moderate stimulation of 5-HT1A receptors with or without the influence of antipsychotic drugs would ameliorate sensorimotor deficits in psychosis-like states (Bubenikova-Valesova et al 2007b;Sumiyoshi et al 2008). Furthermore, we sought to determine whether the effect of tandospirone on these behavioural measures is blocked by WAY 100635, an antagonist at 5-HT1A receptors, and whether an interaction occurs between tandospirone and the typical antipsychotic drug haloperidol, which is a dopamine-D2 receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

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Effect of tandospirone, a serotonin-1A receptor partial agonist, on information processing and locomotion in dizocilpine-treated rats

et al. 2010

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These findings suggest that behavioural changes induced by tandospirone are not fully blocked by 5-HT1A antagonists and that tandospirone (5 mg/kg) potentiates the effect of MK-801. Overall, these findings point to an interaction between NMDA and 5-HT(1A) receptors. Part of the effect of tandospirone on locomotor activity may be mediated by the actions of its active metabolites on other neurotransmitter systems.

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Section: Drugsmentioning

confidence: 99%

Section: Apparatus and Behavioural Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of tandospirone, a serotonin-1A receptor partial agonist, on information processing and locomotion in dizocilpine-treated rats

et al. 2010

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“…One of the most translational measurements of sensory gating is a deficit in prepulse inhibition (PPI) (Green and Braff, 2001). Deficits in PPI of the ASR are reported after acute MK-801 exposure (Arai et al, 2008, Bubenikova-Valesova et al, 2007. Sensitisation to PPI deficits is reported to accompany the development of locomotor sensitisation following repeated MK-801 exposure (Schulz et al, 2001).…”

Section: Behavioural Effects Of Mk-801mentioning

confidence: 99%

Neural mechanisms of MK-801 induced sensitisation

Lefevre¹

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Behavioural sensitisation describes the progressive and enduring augmentation of a drug-induced response that develops with repeated exposure. Sensitisation is a putative mechanism in the pathophysiology of drug addiction and neuropsychiatric disorders such as schizophrenia. In rodents, drug-induced behavioural sensitisation has been described for several different drug classes. The neural mechanisms underpinning behavioural sensitisation to most drugs of abuse share similarities, such as NMDA receptor (NMDAR) activation, although not all use the same mechanism of action.The NMDAR antagonist MK-801 can inhibit sensitisation to other drugs of abuse. However, MK-801 also produces behavioural sensitisation to its own hyperlocomotor inducing effects, suggesting that MK-801 sensitisation has a distinctive mechanism of action.The overall aim of my thesis was to investigate the neural mechanisms of behavioural sensitisation to MK-801 in rats. First, I established the effect of drug dose, environmental context, length of withdrawal period and rat strain on the ability of repeated intermittent MK-801 administration to induce behavioural sensitisation. MK-801-induced sensitisation was shown to be dependent on the dose of MK-801, length of withdrawal period and the rat strain. Sensitisation however was not modulated by the environmental context in which MK-801 administration occurred.In the established sensitisation paradigm, a functional and molecular analysis of the nucleus accumbens of rats sensitised to MK-801 was undertaken. Ex vivo slice electrophysiology revealed a decrease in the excitatory synaptic strength in the nucleus accumbens of rats sensitised to MK-801. An LC-MS/MS proteomics approach demonstrated that proteins altered by MK-801 sensitisationwere predominately related to functions including calcium signalling and mitochondrial dysfunction.I also probed the role of corticosterone signalling using a pharmacological and physiological approach. Pharmacological antagonism of the glucocorticoid receptor with RU486 was found to facilitate behavioural sensitisation to MK-801, potentially through its augmenting effect on MK-801 induced corticosterone levels. Following on from this experiment, I showed that pharmacological antagonism of the stress-related kappa opioid receptor with nor-Binaltorphimine did not have the same effect as RU486. Lastly, I also used LY354740, a pharmacological agonist of the metabotropic glutamate receptors, as a preliminary investigation into the role of glutamatergic transmission. Stimulation of these receptors however was without effect on MK-801 sensitisation.ii Using a range of approaches I have elucidated some of the neural mechanisms and adaptations associated with behavioural sensitisation to MK-801. These results predominately show that sensitisation to MK-801 differs from the mechanism of sensitisation to other drugs of abuse. This model could prove useful for studying the role of NMDARs in the pathophysiology of drug addiction and schizophrenia.iii

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The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT1A signalling

et al. 2013

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RationaleSeveral studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new way to achieve antipsychotic-like activity. LSP1-2111, the group III mGlu receptor orthosteric agonist, with a high affinity towards mGlu4 receptors, was previously shown to exhibit antipsychotic-like action in animal models displaying positive symptoms of schizophrenia.ObjectivesHere, we decided to investigate the possible role of LSP1-2111 in models of negative (social interaction) and cognitive (NOR) symptoms of psychosis. We also investigated the involvement of 5-HT1A receptors in the LSP1-2111-induced antipsychotic effects. Apart from the above-mentioned models of negative and cognitive symptoms, MK-801 and amphetamine-induced hyperactivity tests, plus the DOI-induced head twitches in mice as models for positive symptoms of psychosis, were used in this part of the investigations.ResultsLSP1-2111 (0.5, 2, and 5 mg/ kg) dose-dependently inhibited MK-801-induced deficits in social interaction and NOR tests. The effects of the drug were antagonized by 5-HT1A antagonist, WAY100635 (0.1 mg/kg). A similar inhibition of LSP1-2111-induced effects was observed in models of positive symptoms of schizophrenia. Moreover, the concomitant administration of subeffective doses of LSP1-2111 (0.3-0.5 mg/kg) with a subeffective dose of 5-HT1A agonist, (R)-(+)-8-Hydroxy-DPAT (0.01 mg/kg), induced a clear antipsychotic-like effect in all of the procedures used.ConclusionsAltogether, we propose that the activation of group III mGlu receptors may be a promising target for the development of novel antipsychotic drugs, towards not only positive but also negative and cognitive symptoms. The action of the compound is 5-HT1A-dependent.

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The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801

Cited by 21 publications

References 34 publications

Effect of tandospirone, a serotonin-1A receptor partial agonist, on information processing and locomotion in dizocilpine-treated rats

Effect of tandospirone, a serotonin-1A receptor partial agonist, on information processing and locomotion in dizocilpine-treated rats

Neural mechanisms of MK-801 induced sensitisation

The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT1A signalling

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