Concurrent LI-rTMS induces changes in c-Fos expression but not behavior during a progressive ratio task with adult ephrin-A2A5-/- mice.

Moretti J., Poh EZ., Bolland SJ., Harvey AR., Albrecht MA., Rodger J.

Changes within the dopaminergic system induced by repetitive transcranial magnetic stimulation (rTMS) may contribute to its therapeutic effects; however, dopamine-related behavioral effects of rTMS have not been widely investigated. We recently showed that ephrin-A2A5-/- mice completed significantly fewer trials in a visual task than wildtype mice, and that concurrent low-intensity (LI-) rTMS during the task could partially rescue the abnormal behavior [Poh et al. 2018, eNeuro, vol. 5]. Here, we investigated whether the behavioral differences in ephrin-A2A5-/- mice are due to abnormal motivation, primarily a dopamine-modulated behavior, and whether LI-rTMS would increase motivation. Ephrin-A2A5-/- and wildtype mice underwent 14 daily sessions of progressive ratio (PR) tasks and received either sham or LI-rTMS during the first 10 min. Ephrin-A2A5-/- mice responded more than wildtype comparisons, and LI-rTMS did not influence task performance for either strain. Therefore concurrent stimulation does not influence motivation in a PR task. However, ephrin-A2A5-/- mice did have abnormal performance in the PR tasks after a change in the PR schedule which suggests perseverative behavior. We stained for c-Fos in the prelimbic area (PrL), ventral tegmental area and nucleus accumbens (NAc) core and shell to examine neuronal activity from the final PR session. Sham ephrin-A2A5-/- mice had lower c-Fos expression in the PrL and NAc vs. wildtype mice. Ephrin-A2A5-/- mice that received LI-rTMS showed c-Fos expression closer to wildtype levels in the NAc. Combined with high PR performance, ephrin-A2A5-/- mice show an abnormal shift to habitual responding and LI-rTMS may attenuate this shift.

DOI

10.1016/j.bbr.2020.113011

Type

Journal article

Publication Date

2021-02-26T00:00:00+00:00

Volume

400

Keywords

Animal models, Ephrin, Motivation, Progressive ratio, c-Fos, rTMS, Animals, Behavior, Animal, Ephrin-A2, Ephrin-A5, Female, Habits, Male, Mice, Mice, Inbred C57BL, Motivation, Proto-Oncogene Proteins c-fos, Psychomotor Performance, Reward, Transcranial Magnetic Stimulation

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