Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment

Lins, Brittney R.; Phillips, Anthony G.; Howland, John G.

doi:10.1007/s00213-015-4064-1

Cited by 19 publications

(34 citation statements)

References 48 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed MK-801 treatment increased the number of correction trials completed by the rats, suggesting MK-801 hindered the ability to inhibit incorrect response selection. These findings replicate MK-801-induced perseveration in a variety of other rodent paradigms (Cohn et al 1992;Tuplin et al 2015;Lins et al 2015).…”

Section: Discussionsupporting

confidence: 75%

“…Similarly, the administration of SNP 4 h prior to the TUNL task trended toward reducing the number of correction trials (p=0.063, η=0.212), suggesting that SNP may reduce perseverative behavior (Lins et al 2015). Taken together, this study is the first to demonstrate SNP may have intrinsic properties that facilitate pattern separation and reduce perseveration.…”

Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pamentioning

confidence: 54%

“…It is hypothesized that acute MK-801 administration will disrupt TUNL task performance and reduce accuracy on trials with 2 s and 6 s delays and face validity of MK-801 in the TUNL task will be demonstrated. Further, previous studies have identified perseverative errors following MK-801 administration (Lins et al 2015), and we expect MK-801 will increase the number of correction trials completed by a rat during the TUNL task.…”

Section: Rationale and Hypothesesmentioning

confidence: 69%

“…In rodents, acute MK-801 treatment demonstrates face validity as a model of schizophrenia as its administration produces behavioral changes similar to those observed in the disease (Nestler and Hyman 2010). The acute administration of MK-801 results in locomotor hyperactivity (Howland et al 2012;Mahmood et al 2016), reduced sociability (Morales and Spear 2014), and performance deficits on touchscreen-based (Kumar et al 2015b;Kumar et al 2015a;Lins et al 2015;Lins and Howland 2016) and working memory (Homayoun et al 2004;Galizio et al 2012) tasks. One published study has explored the changes following acute MK-801 (0.05 mg/kg) administration in the TUNL task (Kumar et al 2015a).…”

Section: Discussionmentioning

confidence: 95%

“…The present study is the first to analyze the effects of MK-801 on correction trials. Previous studies utilizing touchscreen tasks in rodents have identified correction trials as a measure of perseveration (Lins et al 2015;Lins and Howland 2016), a behavior frequently observed in patients with schizophrenia (Szoke et al 2008;Ortuño et al 2009). We observed MK-801 treatment increased the number of correction trials completed by the rats, suggesting MK-801 hindered the ability to inhibit incorrect response selection.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Snp Did Not Block Mk-801-induced Impairments But Improved Pamentioning

confidence: 54%

Section: Rationale and Hypothesesmentioning

confidence: 69%