Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat—a back translational study

Goetghebeur, Pascal; Dias, Rebecca

doi:10.1007/s00213-008-1132-9

Cited by 92 publications

(109 citation statements)

References 54 publications

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“…This deficit in also seen in patients with schizophrenia and in our first episode study (Saleem et al, 2010), strengthening the validity of this model in rats. This result is supported by several studies in other laboratories in which sub-chronic PCP also produces deficits in the EDS phase of the attentional set-shifting task, although ours is the only study to use female rats (Rodefer et al, 2005;Goetghebeur and Dias, 2009;Egerton et al, 2008). In the current study PNU-120596 (10 mg/kg) significantly reversed this PCP-induced deficit in the EDS phase.…”

Section: Discussionsupporting

confidence: 89%

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats

et al. 2011

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The α7 nicotinic acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Adult female hooded-Lister rats received sub-chronic PCP (2 mg/kg) or vehicle i.p. twice daily for seven days, followed by 7-days washout. PCP-treated rats then received PNU-120596 (10 mg/kg; s.c.) or saline and were tested in the attentional set-shifting task. Sub-chronic PCP produced a significant cognitive deficit in the extra-dimensional shift (EDS) phase of the task (P<0.001, compared with vehicle). PNU-120596 significantly improved performance of PCP-treated rats in the EDS phase of the attentional set-shifting task (P<0.001). In conclusion, these data demonstrate that PNU-120596 improves cognitive dysfunction in our animal model of cognitive dysfunction in schizophrenia, most likely via modulation of α7 nACh receptors.

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Section: Discussionsupporting

confidence: 89%

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats

et al. 2011

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“…In contrast, Rodefer and colleagues subsequently found that clozapine and risperidone to be ineffective in reversing the PCP-induced deficit, however sertindole and the selective 5-HT 6 (SB-271046) and 5-HT 2A (M100907) receptor antagonists did attenuate the PCP-induced impairment (Rodefer et al, 2008), which is similar to our findings using reversal learning paradigm (Idris et al 2010). This same dosing regime was shown again in male hooded-Lister rats to produce deficits in the EDS phase; an effect which was ameliorated by sertindole and the anti-narcoleptic drug modafinil but not by risperidone or haloperidol (Goetghebeur and Dias, 2009). Egerton and co-workers also used a sub-chronic PCP regime in male Long-Evans rats (2.6 mg/kg daily, i.p., for 5 days followed by a 3 day washout period) and found a strong tendency towards a deficit in the EDS phase of the task (Egerton et al, 2008).…”

Section: Attentional Set-shiftingmentioning

confidence: 81%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

467

319

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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“…These latter strains have been shown to acquire cognitive tests faster and more reliably (Andrews et al, 1995). For this reason, the NOR test was validated using LH rats Redrobe et al, 2010), and the ID-ED test was validated with either LH (Goetghebeur and Dias, 2009) or LE rats (Rodefer et al, 2008). However, only the LE rat strain was available in the People's Republic of China, so it was selected for use in the ID-ED test.…”

Section: Subjectsmentioning

confidence: 99%

Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

Maeda¹,

Lerdrup²,

Sugino³

et al. 2014

J Pharmacol Exp Ther

107

112

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Brexpiprazole piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator with partial agonist activity at serotonin 1A (5-HT 1A ) and D 2/3 receptors, combined with potent antagonist effects on 5-HT 2A , a 1B -, and a 2C -adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response (ED 50 = 6.0 mg/kg), apomorphine-or D-amphetamine-induced hyperactivity (ED 50 = 2.3 and 0.90, respectively), and apomorphine-induced stereotypy (ED 50 = 2.9) in rats at clinically relevant D 2 receptor occupancies. Brexpiprazole also potently inhibited apomorphine-induced eye blinking in monkeys. The results suggest that brexpiprazole has antipsychotic potential. Brexpiprazole induced catalepsy (ED 50 = 20) well above clinically relevant D 2 receptor occupancies, suggesting a low risk for extrapyramidal side effects. Subchronic treatment with phencyclidine (PCP) induced cognitive impairment in both novel object recognition (NOR) and attentional set-shifting (ID-ED) tests in rats. Brexpiprazole reversed the PCP-induced cognitive impairment in the NOR test at 1.0 and 3.0 mg/kg, and in the ID-ED test at 1.0 mg/kg. However, aripiprazole (10 mg/kg) was ineffective in both tests, despite achieving relevant D 2 occupancies. In the NOR test,

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Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat—a back translational study

Abstract: Overall, these findings further support that the rat ID-ED test in subchronic PCP-treated rats has utility and validity as a preclinical model of the cognitive symptoms of schizophrenia and demonstrates back-translational potential.

Cited by 92 publications

References 54 publications

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

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