Sensitivity of the Five-Choice Serial Reaction Time Task to the Effects of Various Psychotropic Drugs in Sprague-Dawley Rats

Paine, Tracie A.; Tomasiewicz, Hilarie C.; Zhang, Kaixuan; Carlezon, William A.

doi:10.1016/j.biopsych.2006.11.017

Cited by 99 publications

(100 citation statements)

References 47 publications

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“…Acute administration of MK-801 (0.008 -0.25mg/kg i.p.) in male Sprague-Dawley rats produced a profile similar to the behavioural impairment that results from acute PCP exposure, namely a reduction in response accuracy coupled with an increase in the number of omissions and premature responding (Paine et al, 2007;Paine & Carlezon, 2009). Amitai et al, (2007) reviewed the effects of several FGAs and SGAs, including haloperidol, clozapine, olanzapine, risperidone, and quetiapine, on the performance in the 5-CSR task, without previously impairing performance via pharmacological means or manipulating test parameters, in male Wistar rats.…”

Section: Systemic Administration Of An Nmda Receptor Antagonistmentioning

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

475

322

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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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Section: Systemic Administration Of An Nmda Receptor Antagonistmentioning

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

475

322

View full text Add to dashboard Cite

show abstract

“…Given the limited size and processing capacity of the frontal cortex in mice and rats vs. primates, and its relatively weaker contribution to the organization of behavior, there is reason to be skeptical that rodent models of higher cognitive processes will provide meaningful homology to human cognition. Nonetheless, mice and rats are amenable to complex conditioning schedules and are capable of performing choices and sophisticated behavioral sequences, and it is certain that studies will assess the potential relationship of PPI to these processes (e.g., Roegge et al 2007;Depoortere et al 2007a, b;Garner et al 2007;Paine et al 2007). Extrapolating these findings to humans will present many challenges.…”

Section: Treatmentmentioning

confidence: 99%

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

et al. 2008

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Introduction Under specific conditions, a weak lead stimulus, or "prepulse", can inhibit the startling effects of a subsequent intense abrupt stimulus. This startle-inhibiting effect of the prepulse, termed "prepulse inhibition" (PPI), is widely used in translational models to understand the biology of brain based inhibitory mechanisms and their deficiency in neuropsychiatric disorders. In 1981, four published reports with "prepulse inhibition" as an index term were listed on Medline; over the past 5 years, new published Medline reports with "prepulse inhibition" as an index term have appeared at a rate exceeding once every 2.7 days (n=678). Most of these reports focus on the use of PPI in translational models of impaired sensorimotor gating in schizophrenia. This rapid expansion and broad application of PPI as a tool for understanding schizophrenia has, at times, outpaced critical thinking and falsifiable hypotheses about the relative strengths vs. limitations of this measure. Objectives This review enumerates the realistic expectations for PPI in translational models for schizophrenia research, and provides cautionary notes for the future applications of this important research tool. Conclusion In humans, PPI is not "diagnostic"; levels of PPI do not predict clinical course, specific symptoms, or individual medication responses. In preclinical studies, PPI is valuable for evaluating models or model organisms relevant to schizophrenia, "mapping" neural substrates of deficient PPI in schizophrenia, and advancing the discovery and development of novel therapeutics. Across species, PPI is a reliable, robust quantitative phenotype that is useful for probing the neurobiology and genetics of gating deficits in schizophrenia.

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“…The primary indicator that CRF disrupted performance in these studies is a decrease in the percentage of correct responses. CRF also increased the percentage of trials in which the rats failed to respond (omission errors) and increased the latency to make a correct response, an effect that may reflect reduced speed of processing or decision making (Robbins, 2002;Paine et al, 2007;Nemeth et al, 2010). The fact that CRF increased the time required to complete the task (ie, collect 90 rewards before the end of the 30-min test session) likely reflects the accumulation of 5-s timeout periods after omitted responses and the small but significant increases in decision-making time over the course of the session.…”

Section: Kor Antagonism Blocks Crf Effects On Attentionmentioning

confidence: 99%

“…Cognitive behavior was quantified using the 5-choice serial reaction time task (5CSRTT), a food-motivated test that is analogous to the continuous performance task used to study attention in humans (Rosvold et al, 1956;Robbins, 2002). The 5CSRTT yields metrics that quantify attention, reaction time, motivation, and impulsivity (Robbins, 2002;Paine et al, 2007;Nemeth et al, 2010). Stress is known to degrade performance in tasks requiring attention or concentration in humans (Campeau et al, 2011), and poor concentration is one of the diagnostic criteria for stress-related psychiatric illnesses such as PTSD (American Psychiatric Association, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Corticotropin-Releasing Factor (CRF)-Induced Disruption of Attention in Rats Is Blocked by the κ-Opioid Receptor Antagonist JDTic

Veer

Yano

Carroll

et al. 2012

Neuropsychopharmacol

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Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggests that corticotropin-releasing factor (CRF) plays an important role in regulating the effects of stress. CRF administration produces stress-like effects in humans and laboratory animals, and CRF levels are elevated in individuals with stress-related illness. Recent work indicates that k-opioid receptor (KOR) antagonists can block CRF effects, raising the possibility that at least some of the effects of stress are mediated via KORs. Here we examined the effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT), a test used to quantify attention in rodents, as well as functional interactions between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and then each was implanted with an intracerebroventricular (ICV) cannula. After recovery and restabilization of performance, they received a single intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist with long-lasting (414 days) effects. In subsequent sessions, rats received ICV infusions of CRF (0.25-1.0 mg) or vehicle and were tested 60 min later. CRF dose-dependently disrupted performance as reflected by decreases in correct responding, increases in omission errors, increases in latencies to respond correctly, and increases in time to complete the session. JDTic attenuated each of these CRF-induced deficits while having no effects on its own. The persistent ability of JDTic to disrupt KOR function was confirmed using the tail immersion assay. These findings indicate that KOR antagonists can prevent acute stress-related effects that degrade performance in tasks requiring attention.

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Sensitivity of the Five-Choice Serial Reaction Time Task to the Effects of Various Psychotropic Drugs in Sprague-Dawley Rats

Cited by 99 publications

References 47 publications

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

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

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

Corticotropin-Releasing Factor (CRF)-Induced Disruption of Attention in Rats Is Blocked by the κ-Opioid Receptor Antagonist JDTic

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