抗精神病药对大鼠母性行为的影响及其机制

Antipsychotic Drugs on Maternal Behavior in Rats and the Underlying Mechanisms

母性行为是一个复杂的本能行为,可以作为研究药物影响社会行为的一个有效模型。人和动物的母性行为具有很多相似的特征。很多临床上用的抗精神病药物,像氟哌啶醇、氯氮平、利培酮、奥氮平、奎硫平、阿立哌唑和氨磺必利都会破坏一种或几种母性反应(比如:幼鼠叼回、舔幼鼠、筑巢行为等)。在阐述产生母性行为的生物学机制的基础上,我们综述了近年来抗精神病药对母性行为的影响及其神经生理机制,并且讨论了这些前临床研究的潜在临床意义。我们认为抗精神病药主要是通过抑制母性动机来影响母性行为的主动成分。非典型抗精神病药引起的镇静对于母性行为的破坏起了重要作用。受体机制上,典型抗精神病药破坏母性行为主要是通过抑制D2受体,而非典型抗精神病药则主要通过抑制5-HT2A/2C受体。包括伏隔核壳区在内的相关奖赏环路是抗精神病药影响母性行为的主要神经网络。这一系列的研究不仅增加了对调控母性行为神经化学机制的理解,也有助于理解抗精神病药的治疗范围及其副作用,并帮助我们理解抗精神病药对人类母性关怀的影响及机制,改善或减弱抗精神病药所带来的消极影响,以便提出更好治疗精神病的方法。

Rat maternal behavior is a complex instinct behavior, which can be used as an effective model to study how drugs influence social behavior. Humans and animals have many similar characteristics. Many clinically used antipsychotic drugs such as haloperidol, clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride disrupt maternal responses （e.g. pup retrieval, pup licking and nest building） to various extents. We present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. We also discuss the potential clinical implications of such preclinical studies for the understanding of the quality of human maternal care in schizophrenic patients who are treated with antipsycbotic medications. We argue that antipsychotic drugs disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drugs-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Dopamine D2receptors and serotonin 5-HT2A/2C receptors are critically involved in 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 line of research is not only important for enhancing our understanding of the neurochemical basis of maternal behavior, but also valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotic treatment. Studying the behavioral effects of antipsychotic drugs on maternal behavior could also help us understand the eAxtent and mechanisms of impacts of antipsyehotic medications on human maternal care. This knowledge may facilitate the development of effective behavioral or other intervening strategies to help patients coping with such undesirable effects.