Background: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium’s ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR – with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. Methods: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother’s brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. Results: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. Conclusion: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat’s maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.
Neuropsychobiology

中文翻译：

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鸦片对孕产妇行为动力学的影响：测试神经化学模型

背景：由于行为的复杂性以及涉及的神经递质和激素系统的多样性，对阿片类药物成瘾的神经化学机制的研究很困难。本研究的目的是使用神经化学模型功能性气质集合 (FET) 的框架和在怀孕期间吸食鸦片的情况下的母亲行为示例，检查对这些机制进行结构化分析的好处。FET 区分 (a) 耐力、(b) 整合速度和 (c) 行为的情绪方面，表明这些系统受 (a) 血清素-神经肽-脑源性神经营养因子 (BDNF)、（b ) 多巴胺-GABA，和 (c) 阿片受体系统，相应地。FET 还表明，与内啡肽（包括鸦片的成分吗啡）结合的 mu-阿片受体 (MOR) 与调节耐力有更强的关联，而 delta-OR 与行为和 kappa-OR 的整合有更强的关联——感知动员在焦虑中看到。为了测试该模型的预测，我们比较了大量 MOR 失调对行为的 3 个行为方面以及血清素、BDNF 和皮质酮水平的影响。方法：本研究选用24只雌性白色Wistar大鼠，随机分为（1）对照组：妊娠大鼠，不进行任何干预；(2)鸦片暴露组：在妊娠期间和分娩后直至研究结束时暴露于鸦片的动物。在研究结束时，评估了母亲大脑海马中BDNF、5-羟色胺（5-HT）和血清皮质酮的水平，以及母亲行为的12个方面。使用独立样本的t检验评估对照组和实验组之间的差异。结果：吸食鸦片的母鼠海马区BDNF和5-羟色胺浓度低于对照组；暴露母亲的平均皮质酮高于对照组。在行为上，吸食鸦片的母亲在 4 个不同的行为类别（筑巢、喂食、梳理和取回）中的耐力低于对照组的母亲。行为整合的难易程度受到的影响较小，仅在 5 项应用措施中的 1 项中显示出显着影响。被视为与情绪相关的行为方面的自我修饰没有受到影响。结论：我们实验中孕期鸦片暴露主要降低了大鼠母性行为的耐受性，但对行为行为的整合速度影响较小。鸦片对耐力的这种负面影响与海马体中 BDNF 和血清素水平的降低以及吸食鸦片的母亲的皮质酮水平升高有关。鸦片暴露对自我美容行为没有影响。与κ和δ阿片受体相比，这种模式支持关于5-HT和BDNF在耐力、耐力的差异调节、行为的综合和情绪方面以及MOR系统与耐力方面的差异关联的FET假设.
神经心理生物学