The pharmacological sensitivity of a touchscreen-based visual discrimination task in the rat using simple and perceptually challenging stimuli

Talpos, John C.; Fletcher, A. C.; Circelli, C.; Tricklebank, Mark D.; Dix, Sophie

doi:10.1007/s00213-011-2590-z

Cited by 43 publications

(37 citation statements)

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“…Taken together, reduced latency and an increased number of total trials completed suggests performance impairments on the TUNL task were not due to impediment of the physical ability to perform the task. Other studies have determined MK-801 does not impair visual perception at doses similar to those used here (Talpos et al 2012), thus it is unlikely performance deterioration was a consequence of perceptual changes. The present experiment suggests acute MK-801 administration in rodents is capable of reducing the ability to resolve spatial patterns and maintain information across a delay.…”

Section: Discussionsupporting

confidence: 58%

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

et al. 2016

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The cognitive symptoms observed in schizophrenia are highly prevalent and predictive of patient functional outcome but are not usually alleviated by conventional antipsychotics. In a recent pilot study, sodium nitroprusside (SNP), a nitric oxide donor, was identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients.Adjunctive SNP has also been reported to decrease the positive and negative symptoms experienced by patients for weeks following a single administration. The mechanisms underlying these changes and the areas of cognition affected remain largely unknown.Therefore, it is of interest to examine the effects of SNP using a rodent model of schizophrenia that has demonstrated predictive validity. The aim of the present experiment was to explore the effects of SNP on the acute MK-801 rodent model of schizophrenia using a highly translatable task in order to establish its validity. Working memory and pattern separation were measured using the trial-unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Acute MK-801 administration 25 minutes prior to task initiation impaired both areas of cognition. When SNP and MK-801 were administered within 5 minutes of each other, no interaction was observed. Interestingly, SNP improved performance on trials with difficult to discriminate patterns (p=0.058). Previous rodent studies using the ketamine model of schizophrenia and the novel object preference task observed a preventative effect of SNP administration. When we administered SNP nearly 4 hours prior to MK-801, no cognitive improvements were observed. Our results suggest that SNP may have intrinsic cognitive enhancing properties but is not capable of reducing MK-801-induced working memory and pattern separation impairments in the TUNL task. This study failed to mirror the results of the human pilot study that observed improved working memory following SNP administration.iii Further, it did not replicate previous animal studies using ketamine. Ultimately, the findings suggest that the effects of MK-801 in the TUNL task may not hold the predictive validity needed for its use in the study of SNP. In order to advance the understanding of SNP, future studies should investigate other translatable paradigms to establish validity. iv ACKNOWLDGEMENTSFirst and foremost, I would like to thank my supervisor Dr. John Howland, for his guidance and encouragement over the past three years. He believed in my abilities before I had proven them to myself and pushed me to be the best scientist and student I could be. John has provided me with countless opportunities to grow as a researcher and selflessly helped me make decisions about my future. I would not be where I am today without him and will always be grateful to have had such an incredible mentor in my life.I would like to thank my committee members, Dr.

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Section: Discussionsupporting

confidence: 58%

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

et al. 2016

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“…Pre-training A standard pre-training procedure was used as described previously by Talpos et al (2012Talpos et al ( , 2014. Briefly, rats were maintained at 85-90 % of their free-feeding body weight (Purina, 15 g/rat) for several days prior to the commencement of habituation and training.…”

Section: General Proceduresmentioning

confidence: 99%

Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation

et al. 2015

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“…In contrast, the NMDA receptor antagonist ketamine, for unknown reasons, did not affect PAL performance in rats (Talpos et al 2014) but in subhuman primates (Taffe et al 2002), while in humans the effects of NMDA receptor antagonists have not yet been tested. Previous studies using a related touchscreen-based simple visual discrimination task demonstrate that MK801 at 0.1 mg/kg but at not lower doses reduced choice accuracy and increased response and magazine latencies (Talpos et al 2012). These findings point to the possibility that MK801 effects on choice accuracy in this simple visual discrimination task could be secondary to nonspecific drug effects.…”

mentioning

confidence: 61%

“…However, in the complex version of the touchscreen-based visual discrimination task that involves morphed stimulus pairs, MK801, like amphetamine, dose-dependently impaired choice accuracy. However, there was no dose × perceptual complexity interaction suggesting that MK801 did not affect visual discrimination (Talpos et al 2012). Of note, in well-trained rats, intrahippocampal microinfusion of MK-801 markedly reduced the number of correct responses in the PAL task used here but not in a simpler PAL task version with lower cognitive but similar perceptual demands (Talpos et al 2009).…”

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confidence: 65%

“…The findings by Talpos et al (2014) and our findings imply that impaired choice accuracy seen here may not be secondary to amphetamine-induced behavioral activation or enhanced impulsivity (Cole and Robbins 1987), effects that might have altered response or magazine latencies. Of note, in a touchscreen-based complex visual discrimination task that, by using morphed stimulus pairs, involved increasing levels of perceptual demands, amphetamine dose-dependently impaired choice accuracy (Talpos et al 2012). Of note, there was no dose × perceptual complexity interaction.…”

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confidence: 99%

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Stimulant drug effects on touchscreen automated paired-associates learning (PAL) in rats

2016

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Here we tested in rats effects of the procognitive drugs modafinil and methylphenidate on post-acquisition performance in an object -location paired-associates learning (PAL) task. Modafinil (32; 64 mg/kg) was without effect, while higher (9 mg/ kg) but not lower (4.5 mg/kg) doses of methylphenidate impaired PAL performance. Likewise, higher but not lower doses of amphetamine (0.4; 0.8 mg/kg) and MK-801 (0.08; 0.12 mg/kg) decreased PAL performance. Impaired PAL performance induced by methylphenidate, amphetamine, and MK801 most likely reflects compromised cognitive function, e.g., retrieval of learned paired associates. Our data suggest that stimulant drugs such as methylphenidate and modafinil might not facilitate performance in hippocampus-related cognitive tasks.[Supplemental material is available for this article.]Touchscreen equipped operant boxes represent a powerful tool to study cognition in rats. This methodology provides superior translational potential because a number of different cognitive tasks can be run that mirror touchscreen methods being part of the Cambridge Neuropsychological Test Automated Battery (CANTAB) used to test human subjects. For instance, the pairedassociates learning task (PAL) allows to investigate learning of object-location associations in rodents and humans Mar et al. 2013;Talpos and Steckler 2013;Josey and Brigman 2015). In rats, post-acquisition performance on the PAL task is sensitive to hippocampal dysfunction. For instance, intrahippocampal microinfusions of lidocaine or NMDA and AMPA receptor antagonists impaired PAL performance in animals that acquired the task before (Talpos et al. 2009). Likewise, in mice, post-acquisition intrahippocampal microinfusions of muscimol impaired PAL performance (Kim et al. 2015). In humans, PAL task performance is predictive of the conversion from mild cognitive dysfunction to Alzheimer's disease (Blackwell et al. 2004). Furthermore, in mild cognitive impairment, PAL performance was correlated with hippocampal volume (Keri et al. 2012).To date, little is known about effects of procognitive drugs on PAL performance. The few available data show that, in mice, the cholinesterase inhibitor donezepil (0.3 mg/kg, i.p.) facilitated PAL performance (Bartko et al. 2011). In contrast, the effects of two other prominent procognitive drugs, methylphenidate and modafinil, in PAL have not been tested yet. Modafinil facilitated performance in a number of rodent cognitive tasks (Beracochea et al. 2001(Beracochea et al. , 2002(Beracochea et al. , 2003Shuman et al. 2009), e.g., enhanced visual discrimination and visual sustained attention (Morgan et al. 2007). Likewise, methylphenidate improved acquisition and retention of spatial memory in maze tasks (Carmack et al. 2014). Both drugs seem to be used as cognitive enhancers for nonmedical purposes (McCabe et al. 2005). However, for both drugs, evidence in favor of cognitive enhancement in humans is mixed (Repantis et al. 2010). For instance, in healthy individuals, methylphenidate and modafinil did not imp...

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The pharmacological sensitivity of a touchscreen-based visual discrimination task in the rat using simple and perceptually challenging stimuli

Abstract: These data improve our understanding of the basic neuropharmacology of a visual discrimination in cognitive tests employing touchscreens and will aid in the interpretation of pharmacological studies with more cognitively demanding methodologies.

Cited by 43 publications

References 55 publications

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation

Stimulant drug effects on touchscreen automated paired-associates learning (PAL) in rats

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