Antipsychotic drugs on maternal behavior in rats

Abstract

Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride, all disrupt active maternal responses (e.g. pup retrieval, pup licking and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at the clinical relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, while 5-HT2A/2C receptors contributing more to atypical drug-induced disruption. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps to understand the extent and mechanisms of impacts of antipsychotic medications on human maternal care, but also is important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects.

Depression‐related disturbances in rat maternal behaviour are associated with altered monoamine levels within mesocorticolimbic structures

“…In parallel, compelling evidence indicates that the mesocorticolimbic monoamine systems facilitate early aspects of mother‐infant attachment, social memory, and motivation in rats and humans . Interference with dopaminergic, noradrenergic and/or serotonergic signalling severely impacts the onset and early expression of maternal behaviour . However, little is known about whether (and how) these monoaminergic systems change throughout the postpartum period to support parenting.…”

“…[22][23][24][25][26] Interference with dopaminergic, noradrenergic and/or serotonergic signalling severely impacts the onset and early expression of maternal behaviour. 23,[26][27][28][29][30][31][32][33][34] However, little is known about whether (and how) these monoaminergic systems change throughout the postpartum period to support parenting.…”

Psychological and neurobiological mechanisms underlying the decline of maternal behavior

“…The MPOA's communication with the mesolimbic dopamine system is particularly important for maternal motivation, consistent with the well documented role of dopamine in reward processing and incentive motivation (Berridge, 2007;Berridge and Robinson, 1998). Functional disturbances of the mesolimbic systems, either enhancing or suppressing dopamine neurotransmission, disrupt maternal behavior, especially the active components of maternal behavior (e.g., pup retrieval, licking), but not passive ones (e.g., high-arched-back nursing) (Hansen, 1994;Li, 2015;Li and Fleming, 2003;Olazabal et al, 2013;Pereira and Ferreira, 2006;Pereira et al, 2005;Stern and Keer, 1999;Stolzenberg and Numan, 2011;Zhao and Li, 2009). One influential model proposed by Michael Numan suggests that multimodal pup stimuli processed and integrated in the medial prefrontal cortex (mPFC) activates MPOA neurons that express receptors to parturitional hormones (estrogen, progesterone, oxytocin, etc.)…”

Gestational folic acid supplementation does not affects the maternal behavior and the early development of rats submitted to neonatal hypoxia‐ischemia but the high supplementation impairs the dam's memory and the Na+, K+ ‐ ATPase activity in the pup's hippocampus

“…Contrary to our findings, Gatta et al, (2018) observed a decreased in the activity maternal behavior (measured by feeding, licking, grooming and carrying the pups) during the first 5 days in dams that were submitted to a perinatal stress protocol. It is also known that treatment with antipsychotic during pregnancy disrupt the active components of maternal behavior by decreasing the time feeding the pups and increasing the latency to get the pups and start to build the nest (Li, 2015). In contrast, another study found that a high‐fat diet during pregnancy and lactation increased the time spend nursing the pups and decreased the period that the mothers were resting, indicating that they spent more time with the offspring (Purcell et al, 2011).…”