Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity

Abstract

Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0 mg/kg, sc). Maternal behavior was tested 2 h later, after which rats were sacrificed and brain tissues were collected. Ten brain regions that were either implicated in the action of antipsychotic drugs and/or in the regulation of maternal behavior were examined for c-Fos immunoreactivity. Acute olanzapine treatment dose-dependently disrupted various components of maternal behavior (e.g., pup retrieval, pup licking, nest building, crouching) and increased c-Fos immunoreactivity in the medial prefrontal cortex (mPFC), nucleus accumbens shell and core (NAs and NAc), dorsolateral striatum (DLSt), ventral lateral septum (LSv), central amygdala (CeA) and ventral tegmental area (VTA), important brain areas generally implicated in the incentive motivation and reward processing. In contrast, olanzapine treatment did not alter c-Fos in the medial preoptic nucleus (MPN), ventral bed nucleus of the stria terminalis (vBST) and medial amygdala (MeA), the core brain areas directly involved in the mediation of rat maternal behavior. These findings suggest that olanzapine disrupts rat maternal behavior primarily by suppressing incentive motivation and reward processing via its action on the mesocorticolimbic dopamine systems, other limbic and striatal areas, but not by disrupting the core processes involved in the mediation of maternal behavior in particular.

Antipsychotic drugs on maternal behavior in rats

“…It has been shown that after an acute administration (in non-pregnant animals) haloperidol shows prolonged D 2 -related therapeutic effects and side-effects, whereas the effects of clozapine/risperidone/quetiapine tend to be more transient (Kapur and Seeman, 2001). Additionally, we found that other atypical antipsychotics such as olanzapine, amisulpride and aripiprazole also exhibit a certain degree of inhibition of active maternal responses in a dose-dependent fashion (Li et al , 2005b; Zhao and Li, 2012). Chronic treatment with haloperidol or olanzapine (another widely prescribed atypical antipsychotic drug) via mini-pumps or repeated daily injections also significantly inhibits rat active maternal responses (Li et al , 2005a).…”

Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

“…Maternal behavior tests were performed in the postpartum female rats in the control and morphine-exposed groups as described previously (Zhao and Li, 2012). Detailed procedure has been described in the Supplementary Materials and Methods.…”

“…As the behavioral and hippocampal morphologic changes in the offspring of parental morphine exposure may be due to the maternal care alterations (Kikusui and Mori, 2009), we evaluated maternal behaviors on postpartum days 6-8, as described previously (Zhao and Li, 2012). As shown in Supplementary Figure S2, among the different groups with or without parental morphine exposure, there were no significant differences in the duration of crouching Effect of morphine exposure on offspring via IGF-2 C-Q Li et al ((F (3,15 …”

c-Fos expression in the paternal mouse brain induced by communicative interaction with maternal mates

“…In rats, experimental evidence has revealed that some of these brain regions are involved in promoting the expression of maternal behavior [2,11,19]. Whether c-Fos expression is induced by communicative interaction in the above mentioned brain regions should be determined.…”