TY - JOUR
T1 - Concurrent LI-rTMS induces changes in c-Fos expression but not behavior during a progressive ratio task with adult ephrin-A2A5-/- mice
AU - Moretti, Jessica
AU - Poh, Eugenia Z.
AU - Bolland, Samuel J.
AU - Harvey, Alan R.
AU - Albrecht, Matthew A.
AU - Rodger, Jennifer
PY - 2021/2/26
Y1 - 2021/2/26
N2 - 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.
AB - 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.
KW - Animal models
KW - c-Fos
KW - Ephrin
KW - Motivation
KW - Progressive ratio
KW - rTMS
UR - http://www.scopus.com/inward/record.url?scp=85096402796&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2020.113011
DO - 10.1016/j.bbr.2020.113011
M3 - Article
C2 - 33181182
AN - SCOPUS:85096402796
VL - 400
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
M1 - 113011
ER -