Inhibitory control and response latency differences between C57BL/6J and DBA/2J mice in a Go/No-Go and 5-choice serial reaction time task and strain-specific responsivity to amphetamine.
Among the best-replicated and most heritable endophenotypes of attention-deficit/hyperactivity disorder (ADHD) are deficits in attention, inhibitory response control and larger intra-individual variability in response latencies. Here, we explored the presence of these heritable ADHD endophenotypes in two commonly used inbred mouse strains, C57BL/6J and DBA/2J, and investigated whether treatment with the stimulant amphetamine affected these phenotypes. Both in an operant Go/No-Go task and 5-choice serial reaction time (5-CSRT) task, DBA/2J mice showed reduced inhibitory response control compared with C57BL/6J mice. Mean correct response latencies of DBA/2J mice were slower in both tasks. Analysis of the distribution of correct response latencies suggested similar processing speed, but DBA/2J mice displayed larger intra-individual variability. Amphetamine did not affect inhibition in the Go/No-Go task but increased omission errors. In contrast, in the 5-CSRT task, amphetamine did not affect omission errors but impaired inhibitory response control, specifically in C57BL/6J mice. The dopamine uptake inhibitor, GBR 12909, mimicked this effect and decreased accurate choice, specifically in C57BL/6J mice, indicating that dopamine modulates inhibitory response control and attention in the murine 5-CSRT task. Amphetamine did not affect response distributions in either task. Furthermore, we extended previous reports on differences in the brain dopamine system of DBA/2J and C57BL/6J mice, by showing differential gene expression levels of three dopamine receptors (Drd1, Drd4 and Drd5) in the mPFC. In conclusion, genetic differences between DBA/2J and C57BL/6J mice translate into multiple ADHD-related phenotypes, indicating that these strains are valuable resources to understand genetic mechanisms underlying ADHD-relevant phenotypes.
Loos
Maarten
M
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
Staal
Jorn
J
Schoffelmeer
Anton N M
AN
Smit
August B
AB
Spijker
Sabine
S
Pattij
Tommy
T
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000523:psychology*; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000096:biosynthesis; D013045:Species Specificity
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D011954:Receptors, Dopamine; C043425:vanoxerine; D000661:Amphetamine