Archival ReportMood Disorder Susceptibility Gene CACNA1C Modifies Mood-Related Behaviors in Mice and Interacts with Sex to Influence Behavior in Mice and Diagnosis in Humans
Section snippets
Animals
Founder mice were obtained from Jackson Laboratories (stock number 005783, Bar Harbor, Maine) that had been backcrossed to C57BL/6J for at least seven generations (see Supplement 1 for additional details).
Behavioral Tests
Mice were tested in the open field, home cage activity, hole board, elevated plus maze, light-dark box, novelty-induced hypophagia, stress-induced hyperthermia, sensitization to d-amphetamine, acoustic startle, and forced swim tests (FSTs) using established methods. Minor alterations to the
Baseline Behaviors, Activity, and Exploration
As homozygous deletion of Cacna1c results in embryonic lethality in mice (29), we conducted studies with heterozygous (Cacna1c+/- [HET]) Cacna1c knockout mice and compared these animals with their wild-type (Cacna1c+/+ [WT]) littermates. Western blot analysis confirmed that heterozygous knockout of Cacna1c results in a significant decrease in levels of Cav1.2 without a change in Cav1.3, which is the most likely protein to compensate for such changes (Figure S1 in Supplement 1). As expected,
Discussion
Our data indicate that in male and female mice, Cacna1c haploinsufficiency is associated with decreased exploratory behavior, decreased hyperlocomotion in response to amphetamine, and antidepressant-like behavior in the FST and TST. There are also sex differences in the effects of Cacna1c haploinsufficiency: female mice exhibit more robust attenuation of amphetamine-induced hyperlocomotion than male mice and, unlike male mice, display an attenuated acoustic startle response and reduced
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Authors DTD and PBM and authors JBP and TDG contributed equally to this work.