Profiling attention and cognition enhancing drugs in a rat touchscreen-based continuous performance test
A novel rodent continuous performance test (CPT) was developed as one of the goals of the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium to improve its translatability to the CPT test used in human subjects.
The objective of the study is to investigate the effects of attention and cognition enhancing drugs in rodent CPT.
A single cohort of rats were trained to asymptotic performance in the test. Pharmacological test sessions were then performed twice per week in a full crossover design with the following drugs tested: methylphenidate (0.3, 1, and 3 mg/kg), the α4β2 nicotinic agonist ABT-594 (0.0023, 0.007 and 0.023 mg/kg), modafinil (8, 16, and 32 mg/kg), atomoxetine (0.3, 1, and 3 mg/kg), donepezil (0.1, 0.3, and 1 mg/kg), and memantine (1.25, 2.5, and 5 mg/kg).
The stimulant-like drugs methylphenidate, ABT-594, and modafinil were found to increase measures of impulsivity and overall responding with generally no positive effects on d’, a putative measure of attention, with the exception of ABT-594 which improved d’ at the highest dose tested. Atomoxetine and the memory-enhancing drugs donepezil and memantine, on the other hand, were found to reduce measures of impulsivity and responding and had either negligible or worsening effects on d’.
Our results suggest rodent CPT can detect changes in impulsivity resulting from drugs known to improve attention in rodents and humans. However, additional work is needed to assess the sensitivity and validity of this assay for assessing effects on attention.
KeywordsAttention Cognition Touchscreen operant chamber Continuous performance test Methylphenidate ABT-594 Modafinil Atomoxetine Donepezil Memantine
AbbVie was responsible for the study design, research, analysis, data collection, interpretation of data, and writing, reviewing, and approving of the publication. All authors are current or past employees of AbbVie and may own AbbVie stock.
This work was funded by AbbVie and received support from the NEWMEDS Innovative Medicine Initiative Joint Undertaking grant 115008, composed of EFPIA in-kind contribution and financial contribution from the EU’s 7th Framework Program (FP7/2007-2013).
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