Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.
Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.
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DOI：
10.1038/s41598-023-37696-8
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发表时间：
2023-07-05
影响因子：
4.6
通讯作者：
Bolanos-Guzman, Carlos A. A.
中科院分区：
文献类型：
--
作者：
Cardona-Acosta, Astrid M. M.;Sial, Omar K. K.;Parise, Lyonna F. F.;Gnecco, Tamara;Marti, Giselle Enriquez;Bolanos-Guzman, Carlos A. A.
据报道，青少年中苯二氮卓类药物的使用有所增加，其中滥用最多的是阿普唑仑（ALP）。青少年时期的药物滥用可引起具有持久后果的变化。本研究调查了C57 BL/6J雄性小鼠青春期ALP暴露的神经生物学后果。小鼠每天一次接受ALP（0、0.5、1.0 mg/kg）（出生后第35 - 49天）。吗啡（2.5，5.0毫克/公斤）的反应性的变化，使用条件性位置偏爱范例，ALP暴露后24小时和1个月进行了评估。在另一项实验中，小鼠接受ALP（0，0.5 mg/kg），然后在治疗后24小时或1个月处死，以评估腹侧被盖区（VTA）和延髓核（NAc）内细胞外信号调节激酶1/2（ERK 1/2）基因表达、蛋白磷酸化和下游靶点（CREB，AKT）的水平。ALP预处理的小鼠对与阈下剂量（2.5 mg/kg）莫尔短期配对的隔室产生强烈偏好，并且这种效应也存在于1个月组中。青少年ALP暴露导致VTA-NAc通路内ERK信号转导失调24小时和1个月后ALP暴露。结果表明，青春期ALP暴露增强了莫尔的奖励特性，并诱导VTA-NAc通路内ERK信号传导的持续变化，VTA-NAc通路是一种高度参与药物奖励和情绪相关行为调节的脑回路。
Increased use of benzodiazepines in adolescents have been reported, with alprazolam (ALP) being the most abused. Drug abuse during adolescence can induce changes with lasting consequences. This study investigated the neurobiological consequences of ALP exposure during adolescence in C57BL/6J male mice. Mice received ALP (0, 0.5, 1.0 mg/kg) once/daily (postnatal day 35–49). Changes in responsiveness to morphine (2.5, 5.0 mg/kg), using the conditioned place preference paradigm, were assessed 24-h and 1-month after ALP exposure. In a separate experiment, mice received ALP (0, 0.5 mg/kg) and then sacrificed 24-h or 1-month after treatment to assess levels of extracellular signal regulated kinase 1/2 (ERK1/2) gene expression, protein phosphorylation, and downstream targets (CREB, AKT) within the ventral tegmental area (VTA) and nucleus accumbens (NAc). ALP-pretreated mice developed a strong preference to the compartment(s) paired with a subthreshold dose (2.5 mg/kg) of MOR short-term, and this effect was also present in the 1-month group. Adolescent ALP exposure resulted in dysregulation of ERK-signaling within the VTA-NAc pathway 24-h and 1-month after ALP exposure. Results indicate ALP exposure during adolescence potentiates the rewarding properties of MOR and induces persistent changes in ERK-signaling within the VTA-NAc pathway, a brain circuit highly implicated in the regulation of both drug reward and mood- related behaviors.
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影响因子：
3.4
作者：
Reissig, Chad J.;Harrison, Joseph A.;Carter, Lawrence P.;Griffiths, Roland R.
通讯作者：
Griffiths, Roland R.
影响因子：
3.9
作者：
Guina J;Merrill B
通讯作者：
Merrill B
影响因子：
3.9
作者：
BUSTO, U;SELLERS, EM
通讯作者：
SELLERS, EM
影响因子：
3.3
作者：
FINLAY, JM;ZIGMOND, MJ;ABERCROMBIE, ED
通讯作者：
ABERCROMBIE, ED
影响因子：
11.4
作者：
HENDERSON, A;WRIGHT, M;POND, SM
通讯作者：
POND, SM