Maternal behavior in rats is a highly motivated and well-organized social behavior. It is an ecologically valid animal model for the study of basic psychological processes such as emotion, motivation, reward, learning and memory and social interaction, and has recently been used in modeling postpartum depression and psychosis. The core neural circuits underlying rat maternal behavior have been well elucidated. Recent work has also identified a role of the mesolimbic dopamine system in this behavior. However, considerably less is known about the role of serotonin (5-HT) in maternal care. Given the importance of serotonin in emotion, motivation, social behavior and major depression and its known interaction with dopamine, it is likely that functional disturbances of 5-HT systems would alter the quality of maternal care and may contribute to postpartum depression. One key issue remaining is to identify specific neuroreceptors and the underlying psychological processes through which serotonin act to affect maternal behavior. The Principal Investigator's long-term goal is to understand the behavioral mechanisms and neurobiological basis of maternal behavior. The objective of the proposed R01 project is to delineate the respective roles of 5-HT2A and 5-HT2C receptors in rat maternal behavior and identify their associated psychological processes. Based on preliminary studies and literature review, the Principal Investigator hypothesizes that disturbances of 5-HT2A and 5-HT2C receptor-mediated neurotransmission in the nucleus accumbens shell (NAs) and medial prefrontal cortex (mPFC)-related neural network disrupt maternal behavior. Because 5 -HT2A and 5-HT2C receptors play important yet opposing roles in incentive motivation, aversive processing, and executive controls, it is further hypothesized that activation or blockade of each 5-HT2 receptor alone disrupts maternal behavior. However, activation or blockade of both receptors concurrently will cause no or less disruption due to the antagonistic action between the two. Disturbances of 5-HT2A and 5-HT2C receptors cause maternal behavior deficits by decreasing maternal motivation, increasing negative emotional responses (e.g. fear, avoidance) toward pups, and/or fragmenting pup- directed responses. In the proposed study, Aim 1 will be to determine the effects of systemic injections of selective 5-HT2A and 5-HT2C agonists, antagonists, and their combinations on maternal behavior. Furthermore, the possible psychological processes (e.g. incentive motivation, fear responses, behavioral fragmentation) affected by 5-HT2A and 5-HT2C manipulations will be investigated.
Aim 2 will be to determine the effects on maternal behavior of central infusions of these drugs - alone and in combination - into the NAs, mPFC and dorsolateral striatum. This project addresses an understudied area in maternal behavior. It is innovative in that behavioral, systemic and intracranial pharmacology approaches will be combined to comprehensively investigate the 5-HT receptor mechanisms involved in normal rat maternal behavior. It will help identify the behavioral processes linking altered maternal behavior and postpartum depression.
This preclinical project is designed to determine the important neuroreceptor mechanisms underlying normal maternal behavior in rats and explore their contributions to abnormal postpartum behaviors. Knowledge gained from this project is expected to enhance understanding of behavioral changes caused by disrupted serotonin neurotransmission and how these changes impact the quality of maternal care. Project outcomes are expected to point to a new treatment approach for parenting problems and possibly postpartum depression and - ultimately - positively impact the health and well-being of mothers and their children.
|Gao, Jun; Wu, Ruiyong; Davis, Collin et al. (2018) Activation of 5-HT2A receptor disrupts rat maternal behavior. Neuropharmacology 128:96-105|
|Li, Ming; Chou, Shinn-Yi (2016) Modeling postpartum depression in rats: theoretic and methodological issues. Dongwuxue Yanjiu 37:229-36|
|Zhang, Mengjiao; Li, Ming (2016) Behavioral and pharmacological validation of an integrated fear-potentiated startle and prepulse inhibition paradigm. Behav Brain Res 307:176-85|
|Wu, Ruiyong; Gao, Jun; Chou, Shinnyi et al. (2016) Behavioral, pharmacological and neuroanatomical analysis of serotonin 2C receptor agonism on maternal behavior in rats. Psychoneuroendocrinology 73:252-262|
|Li, Ming (2015) Antipsychotic drugs on maternal behavior in rats. Behav Pharmacol 26:616-26|
|Yang, Yu; Qin, Jingxue; Chen, Weihai et al. (2015) Behavioral and pharmacological investigation of anxiety and maternal responsiveness of postpartum female rats in a pup elevated plus maze. Behav Brain Res 292:414-27|
|Chen, Weihai; Zhang, Qi; Su, Wenxin et al. (2014) Effects of 5-hydroxytryptamine 2C receptor agonist MK212 and 2A receptor antagonist MDL100907 on maternal behavior in postpartum female rats. Pharmacol Biochem Behav 117:25-33|