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. 2013 Aug;228(3):411-8.
doi: 10.1007/s00213-013-3045-5. Epub 2013 Mar 17.

Differential antidepressant-like response to lithium treatment between mouse strains: effects of sex, maternal care, and mixed genetic background

Adem Can  1 , Sean C Piantadosi, Todd D Gould
Affiliations

Differential antidepressant-like response to lithium treatment between mouse strains: effects of sex, maternal care, and mixed genetic background

Adem Can et al. Psychopharmacology (Berl). 2013 Aug.

Abstract

Background: Lithium is a mood stabilizer with both antidepressant and antimanic properties, however its mechanism of action is unclear. Identifying the genetic factors that influence lithium's therapeutic actions will be an important step to assist in identifying such mechanisms. We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain.

Objectives: This study aimed to assess the roles of both genetic and non-genetic factors such as sex and non-shared environmental conditions that may mediate differential behavioral responses to lithium.

Methods: Mice were treated with lithium for 10 days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal. We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains.

Results: Neither sex nor maternal care significantly influenced the differential antidepressant-like response to lithium. Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain but had no effects in BALB/cJ mice. Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain.

Conclusions: Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains. Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium's therapeutic actions.

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Figures

Fig. 1
Fig. 1. Immobility time in the first FST after ten days of lithium treatment and following ten days of withdrawal in male and female C57BL/6J and BALB/cJ mice
Con/Con refers to the groups that received control food in both phases of the experiment; Lit/Con refers to the groups that received lithium chloride containing food in the first ten days of the experiment and then received control food in the second ten days of the experiment. ***p<0.001 denotes a significant difference compared to control group of the treatment phase. Data are expressed as mean±SEM. n=8–16 per group as indicated in the lower portions of the bars.
Fig. 2
Fig. 2. Immobility time in the FST after ten days of lithium treatment in BALB/cJ and C57BL/6J mice cross-fostered to a dam of the same strain (in-fostered) or to the other strain (cross-fostered)
***p<0.001 denotes a significant difference compared to the C57BL/6J control groups. Data are expressed as mean±SEM. n=11–18 per group. In each bar, the female and male numbers for that particular group are indicated.
Fig. 3
Fig. 3. Immobility time in the FST after ten days of lithium treatment in male C57BL/6J and CBF1/J mice
“a” denotes a significant difference compared to the C57BL/6J and CB6F1/J control groups, p<0.001. “b” denotes a significant difference compared to the CB6F1/J lithium group, p<0.05. Data are expressed as mean±SEM. n=12 per group.
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