Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm

Gemperle, A; McAllister, Kevin H.; Olpe, Hans‐Rudolf

doi:10.1007/s00213-003-1459-1

Cited by 24 publications

(9 citation statements)

References 67 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, we chose to study chronic dosing to better reflect the clinical situation. As such, the acute administration studies (Beatty and Rush 1983;Didriksen 1995;Skarsfeldt 1996;Gemperle et al 2003) would not be expected to produce similar results to ours. Secondly, it is possible that investigation of the same effect using different behavioural paradigms can produce different results.…”

Section: Discussioncontrasting

confidence: 71%

“…The effects of antipsychotics on spatial cognitive performance in rats have been studied in other preclinical cognitive models ranging from reference memory spatial place learning tasks in the Morris water maze (Skarsfeldt 1996;Terry et al 2002) to working memory tasks in both the delayed non-matching-to-position operant chamber paradigm (Beatty and Rush 1983;Didriksen 1995;Gemperle et al 2003) and radial maze (Rosengarten and Quartermain 2002). In these previous studies, effects of atypical antipsychotics were varied and depended on the type of cognitive process tested, the paradigm used to do so, the particular antipsychotics used, the duration of antipsychotic treatment, and dosages studied.…”

Section: Discussionmentioning

confidence: 99%

“…To date, there have been few rodent studies investigating the effects of atypical antipsychotics on cognitive function. Previous studies on working memory have yielded mixed results (Didriksen 1995;Schroeder et al 2000;Addy and Levin 2002;Rosengarten and Quartermain 2002;Gemperle et al 2003;Addy et al 2005;Levin et al 2005). Several of these studies have reported detrimental effects of atypical antipsychotic treatment on working memory (Didriksen 1995;Addy and Levin 2002;Rosengarten and Quartermain 2002;Levin et al 2005).…”

Section: Introductionmentioning

confidence: 93%

See 2 more Smart Citations

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

et al. 2007

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In light of the interest in NK 3 receptor antagonism as a potential antipsychotic treatment, it is interesting to note that both typical and atypical antipsychotics have been reported to either worsen delayed nonmatch to position performance delay independently (Didriksen 1995 and data generated in-house at Roche) or leave delayed nonmatch to position performance unaffected in rats (Gemperle et al 2003), though iloperidone has been reported to improve delayed nonmatch to position performance delay dependently (Gemperle et al 2003), and delay-dependent deficits following haloperidol and clozapine intake have been demonstrated in primates (Murphy et al 1996). Furthermore, Fig.…”

Section: Discussionmentioning

confidence: 99%

Cognitive performance in neurokinin 3 receptor knockout mice

et al. 2008

View full text Add to dashboard Cite

Rationale The neurokinin 3 (NK 3 ) receptor is a novel target under investigation for improvement of the symptoms of schizophrenia due to its ability to modulate dopaminergic signaling. However, research on effects of NK 3 antagonism with animal models has been hindered because of species differences in the receptor between humans, rats, and mice. Objectives The aim of the present study is to further knowledge on the role of NK 3 in cognitive functioning by testing the effect of knockout of the NK 3 receptor on tests of working memory, spatial memory, and operant responding. Materials and methods NK 3 knockout mice generated on a C57Bl/6 background were tested in delayed matching to position (DMTP), spontaneous alternation, Morris water maze, and active avoidance tasks. Results NK 3 knockout mice showed better performance in the DMTP task, though not delay dependently, which points to an effect on operant performance but not on working memory. No differences were seen between the groups in spontaneous alternation, another indication that working memory is not affected in NK 3 knockouts. There was no impairment in knockout mice in Morris water maze training, and the mice also showed faster response latency in the active avoidance task during training. Conclusions Collectively, these results support a role for the NK 3 receptor in performance of operant tasks and in spatial learning but not in working memory.

show abstract

“…Most published papers have demonstrated the effect of antipsychotics on cognitive functions of healthy animals (23)(24)(25)(26)(27)(28)(29). The aim of our research was to investigate the impact of 5-HT2A/2C receptor antagonism, alone or in combination with D2 receptor antagonism, on the impairment in a spatial memory task induced by subchronic administration of MK-801.…”

mentioning

confidence: 99%

Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

Bubeníková-Valešová¹,

Stuchlı́k

Svoboda

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Spatial working memory or short-term place memory is impaired in schizophrenia. The efficiency of antipsychotic drugs, particularly of typical antipsychotics, on cognitive deficit in schizophrenia remains disputable. Inhibition of serotonin (5-HT) 2A/2C receptors is important for cognitive improvement in schizophrenic patients treated with antipsychotics. The aim of the present work was to establish the effect of the 5-HT2A/2C receptor antagonist ritanserin (2.5 or 5 mg/kg), the dopamine D2 antagonist haloperidol (0.1 or 1 mg/kg), and the atypical antipsychotic risperidone (0.1 mg/kg or 1 mg/kg), which is an antagonist of both 5-HT2A/2C and D2 receptors, on cognitive deficit induced by subchronic administration of dizocilpine (MK-801, 0.1 mg/kg). We used the active allothetic place avoidance (AAPA) task, requiring the rat to differentiate between relevant and irrelevant stimuli, in a way similar to disruption of information processing disturbed in schizophrenic patients. Our results show that treatment with 5-HT2A/2C receptor antagonists, regardless of their effect on D2 receptors, blocked the cognitive impairment produced by MK-801. Haloperidol did not sufficiently reduce the deficit in AAPA induced by MK-801. Interestingly, administration of risperidone and haloperidol alone, but not ritanserin, impaired the AAPA performance in intact rats. Ritanserin and risperidone actually improve cognition independently of their effect on locomotor activity in an animal model of schizophrenia-like behavior. This finding is in accordance with the assumption that some antipsychotics are primarily effective against cognitive dysfunction in schizophrenia.animal model of schizophrenia ͉ antipsychotics ͉ cognition ͉ MK-801 ͉ spatial memory S chizophrenia is a complex neuropsychiatric illness that affects 1% of the population. In addition to psychotic symptoms, cognitive impairment has been found across all subtypes of the disease (1, 2). It has been established that patients with schizophrenia are deficient in abstraction, executive function, verbal memory, language function, vigilance, and attention (3). Moreover, short-term place memory has been shown to be impaired in schizophrenia (4, 5), and a deficit in spatial working memory has even been proposed as an endophenotype marker for schizophrenia (6).Antipsychotics of all groups alleviate psychotic symptoms of schizophrenia, but the effect of typical antipsychotics on cognitive deficit in schizophrenia remains in dispute (7). It has been suggested that inhibition of serotonin (5-HT) 2A/2C receptors mediates the cognitive improvement of antipsychotic-treated schizophrenic patients (8). The aim of the present work was to establish the effect of the 5-HT2A/2C receptor antagonist ritanserin, the dopamine D2 antagonist haloperidol, and the atypical antipsychotic risperidone, which is an antagonist of both 5-HT2A/2C and D2 receptors, on the cognitive deficit induced by subchronic administration of dizocilpine (MK-801).Acute or chronic administration of NMDA receptor antagonists such...

show abstract

Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm

Abstract: In accordance with their different pharmacological profiles, the three NLs iloperidone, clozapine, and haloperidol have different effects in this preclinical cognitive task. These results might provide important information for the development of NLs with beneficial effects on cognition.

Cited by 24 publications

References 67 publications

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

Cognitive performance in neurokinin 3 receptor knockout mice

Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

Contact Info

Product

Resources

About