成年和青春期抗精神病药暴露会增加雄性C57BL/6小鼠的延迟折现并降低其行为灵活性。

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2024-09-04 DOI:10.1016/j.pbb.2024.173866
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引用次数: 0

摘要

第二代抗精神病药物是青少年的常用处方药,但对其长期使用所产生的后果却研究不足。这些药物通过单胺类神经递质系统发挥作用,尤其是多巴胺和血清素。多巴胺和血清素与许多行为有关,包括冲动选择和行为可塑性。在一个青少年使用抗精神病药物的小鼠模型中,雄性C57BL/6小鼠从出生后第22-60天开始通过饮用水接触2.5毫克/千克/天的利培酮或5毫克/千克/天的奥氮平。为了确定青春期是否对抗精神病药物暴露有独特的敏感性,我们将小鼠行为的长期影响与同等暴露的成年小鼠组进行了比较,后者从出生后第101-138天开始暴露于2.5毫克/千克利培酮。对青春期动物的运动活动和体重进行了评估。暴露30天后,使用空间辨别反转和延迟折现法对终止暴露的动物的行为灵活性和冲动性选择进行评估。在第二次逆转过程中,抗精神病药物暴露对行为灵活性产生了适度的改变。在冲动性选择方面,暴露动物与对照组相比,对延迟替代奖励的贬值程度要高得多。这种效应在青少年和成年动物暴露后都能观察到,表明无论暴露年龄大小,冲动性选择都会发生不可逆转的变化。
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Adult and adolescent antipsychotic exposure increases delay discounting and diminishes behavioral flexibility in male C57BL/6 mice

Second-generation antipsychotics are frequently prescribed to adolescents, but the long-term consequences of their use remain understudied. These medications work via monoamine neurotransmitter systems, especially dopamine and serotonin, which undergo considerable development and pruning during adolescence. Dopamine and serotonin are linked to a wide host of behaviors, including impulsive choice and behavioral plasticity. In a murine model of adolescent antipsychotic use, male C57BL/6 mice were exposed to either 2.5 mg/kg/day risperidone or 5 mg/kg/day olanzapine via drinking water from postnatal days 22–60. To determine whether the adolescent period was uniquely sensitive to antipsychotic exposure, long-term effects on behavior were compared to an equivalently exposed group of adults where mice were exposed to 2.5 mg/kg risperidone from postnatal days 101–138. Motor activity and body weight in adolescent animals were assessed. Thirty days after exposure terminated animal's behavioral flexibility and impulsive choice were assessed using spatial discrimination reversal and delay discounting. Antipsychotic exposure produced a modest change in behavior flexibility during the second reversal. There was a robust and reproducible difference in impulsive choice: exposed animals devalued the delayed alternative reward substantially more than controls. This effect was observed both following adolescent and adult exposure, indicating that an irreversible change in impulsive choice occurs regardless of the age of exposure.

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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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