Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats

Enomoto, Takeshi; Ishibashi, Tadashi; Tokuda, Kumiko; Ishiyama, Takeo; Toma, Satoko; Ito, Akira

doi:10.1016/j.bbr.2007.08.012

Cited by 119 publications

(61 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enomoto et al [5] showed that aripiprazole did not affect animal performance in the Morris water maze and radial-arm maze tests. The authors also observed that the drug showed no ameliorating effect on MK-801-induced impairment of learning and memory in these tasks, which indicated that there was no activity at the NMDA glutamate receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have assessed physiopathologic aspects linked to schizophrenia, such as declarative and nondeclarative memory functions, to identify areas of impairment versus preservation [3] . Similarly, some investigations have evaluated the effect of antipsychotic drugs on cognitive parameters in humans and animals [4,5] . Research suggests that schizophrenic patients treated with atypical antipsychotics may perform better in cognitive tasks when compared to patients treated with typical antipsychotics [2,6] .…”

Section: Introductionmentioning

confidence: 99%

“…The drug was developed recently, and it presents a unique pharmacological profile that includes dopamine D 2 partial agonism, serotonin 5-HT 1A partial agonism, and 5-HT 2A antagonism [5,6] . Clinical trials have found that aripiprazole was effective in treating the positive, negative, and cognitive symptoms of schizophrenia [7] .…”

Section: Introductionmentioning

confidence: 99%

“…In another study, the single or repeated treatment with aripiprazole, but not haloperidol, revealed that aripiprazole was able to ameliorate the cognitive impairment induced by treatment with PCP. This effect was blocked by co-treatment with dopamine D 1 and 5-HT 1A antagonist receptors, suggesting that behavior triggered by aripiprazole can be associated with dopamine D 1 and serotonin 5-HT 1A receptors [9] .Enomoto et al [5] showed that aripiprazole did not affect animal performance in the Morris water maze and radial-arm maze tests. The authors also observed that the drug showed no ameliorating effect on MK-801-induced impairment of learning and memory in these tasks, which indicated that there was no activity at the NMDA glutamate receptors.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

View full text Add to dashboard Cite

Aim: Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D 2 partial agonism, serotonin 5-HT 1A partial agonism and 5-HT 2A antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation. Methods: Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS). Results: Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short-and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected. Conclusion: Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.Keywords: antipsychotic agent; aripiprazole; locomotion; memory; genotoxic/mutagenic activities; DNA damage; lipoperoxidation Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1225Sinica ( -1232 doi: 10.1038/aps.2011 published online 15 Aug 2011 Original Article * To whom correspondence should be addressed. [8] .In the experimental context, Nagai et al [9] showed that aripiprazole that was administered as either a single dose or as consecutive doses (for 7 d) ameliorated phencyclidine-induced impairment of recognition memory in mice. However, another study showed that aripiprazole impaired the passiveavoidance response at doses near its anti-dopamine ED 50 (7.7 mg/kg, as defined by apomorphine stereotypy). At doses lower than those that affected the passive-avoidance response, aripiprazole was unable to reverse the MK-801-induced impairment in the same task [4] . Therefore, further investigations are necessary to elucidate the effect of aripiprazole on memory.The aim of the present study was to investigate the effects of aripiprazole on memory and on locomotor and exploratory activities with the inhibitory avoidance and open field tasks as behavioral models. Some drugs that affect memory can induce damage in biomolecules, such as lipids and DNA. Therefore, possible cytotoxic and genotoxic effects were evaluated by measuring lipid peroxidation in the liver and DNA strand breaks in both the peripheral blood and brain tissues after behavioral tasks. Mutagenic e...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

View full text Add to dashboard Cite

show abstract

“…We also found that the preventive effect of lurasidone lasted at least 14 days after the final PCP injection (on day 22). It has been reported that lurasidone has cognitive benefits in some animal models of CIS, in which other APDs were ineffective or even worsened the impairment in cognition (Ishiyama et al, 2007;Enomoto et al, 2008). Lurasidone was reported to be somewhat more effective than ziprasidone to improve general cognitive function in patients with schizophrenia in a double-blind study of 21 days duration (Harvey et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Horiguchi

Hannaway

Adelekun

et al. 2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Hypoglutamatergic function may contribute to cognitive impairment in schizophrenia (CIS). Subchronic treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), induces enduring deficits in novel object recognition (NOR) in rodents. Acute treatment with atypical antipsychotic drugs (APDs), which are serotonin (5-HT) 2A /dopamine D 2 antagonists, but not typical APDs, eg, haloperidol, reverses the PCP-induced NOR deficit in rats. We have tested the ability of lurasidone, an atypical APD with potent 5-HT 1A partial agonist properties, tandospirone, a selective 5-HT 1A partial agonist, haloperidol, a D 2 antagonist, and pimavanserin, a 5-HT 2A inverse agonist, to prevent the development of the PCP-induced NOR deficit. Rats were administered lurasidone (0.1 or 1 mg/kg), tandospirone (5 mg/kg), pimavanserin (3 mg/kg), or haloperidol (1 mg/kg) b.i.d. 30 min before PCP (2 mg/kg, b.i.d.) for 7 days (day1-7), followed by a 7-day washout (day8-14). Subchronic treatment with PCP induced an enduring NOR deficit. Lurasidone (1 mg/kg) but not 0.1 mg/kg, which is effective to acutely reverse the deficit due to subchronic PCP, or tandospirone, but not pimavanserin or haloperidol, significantly prevented the PCP-induced NOR deficit on day 15. The ability of lurasidone co-treatment to prevent the PCP-induced NOR deficit was enduring and still present at day 22. The preventive effect of lurasidone was blocked by WAY100635, a selective 5-HT 1A antagonists, further evidence for the importance of 5-HT 1A receptor stimulation in the NOR deficit produced by subchronic PCP. Further study is needed to determine whether these results concerning mechanism and dosage can be the basis for prevention of the development of CIS in at risk populations.

show abstract

Antipsychotic Agents

Ablordeppey

Ofori

2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Schizophrenia is one of the most severe diseases of the brain and is characterized by a spectrum of symptoms including positive, negative, and cognitive symptoms. Even though schizophrenia has a low worldwide prevalence (0.4–0.7%), it is one of the most devastating diseases of the central nervous system (CNS). Despite the immense studies on schizophrenia over the years, the exact cause of the disorder remains unknown. Therefore, morbidity studies and their outcomes for schizophrenia continue to rely on descriptive definitions spelled out in the Diagnostic and Statistical Manual of Mental Disorders‐fifth edition (DSM‐5). Current pharmacotherapy of the disease involves the use of antipsychotic agents that target CNS receptors including dopamine and serotonin receptor subtypes. Despite the success in the management of psychiatric illness most of the current antipsychotics are saddled with problems such as inefficacy across patient populations and disease domains and intolerable side effects that limit their widespread utility. Evolving paradigm shift in antipsychotic drug discovery efforts over the last decade has begun to address these issues opening the door for new hypotheses that integrate well‐known neurotransmitter systems with neuronal circuits. Recent advances in molecular biology and genetics are also paving the way for a better understanding of the etiology and pathophysiology of schizophrenia. In addition to reviewing currently used agents, this article will focus on the advances made to address the stated problems and highlight the paradigm shift in the antipsychotic drug discovery area.

show abstract

Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats

Cited by 119 publications

References 34 publications

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Antipsychotic Agents

Contact Info

Product

Resources

About