首页> 外文期刊>The European Journal of Neuroscience >Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats.
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Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats.

机译:产后早期养育条件对成年大鼠中脑皮质多巴胺的影响以及对精神刺激和应激源的行为反应。

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Abstract While many experiment with drugs, relatively few individuals develop a true addiction. We hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, we investigated whether stimulant- and stress-induced activation of nucleus accumbens dopamine transmission and dopamine-dependent behaviours might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non-handled) during the first 14 days of life. We found that, in comparison with their handled counterparts, maternally separated and non-handled animals are hyperactive when placed in a novel setting, display a dose-dependent higher sensitivity to cocaine-induced locomotor activity and respond to a mild stressor (tail-pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non-handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens-core and striatal dopamine transporter sites in maternally separated animals. Interestingly, we also found greatly reduced D(3) dopamine receptor binding and mRNA levels in the nucleus accumbens-shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking.
机译:摘要虽然许多人在尝试毒品,但很少有人会真正上瘾。我们假设,在大鼠中,成瘾药物作用的这种个体差异可能取决于出生后的饲养条件。为了检验这一想法,我们调查了成年大鼠是否反复受到母体长时间分离或短暂处理或不受干扰(无刺激),从而引起刺激和应激诱导的伏伏核多巴胺传递激活和多巴胺依赖性行为的差异。 -处理)在生命的前14天。我们发现,与它们的同龄人相比,母体分离和未操纵的动物在新颖的环境中活动过度,对可卡因诱导的运动活动表现出剂量依赖性的更高敏感性,并对轻度的应激反应有反应(尾巴捏) ),伏隔核中的多巴胺水平显着增加。另外,发现母本分离的动物在未能使经处理和未经处理的动物致敏的条件下反复施加压力时,对苯丙胺的运动刺激作用敏感。最后,定量受体放射自显影显示母本分离的动物中伏伏核核心和纹状体多巴胺转运蛋白位点的密度较低。有趣的是,我们还发现处理的动物伏隔核壳中的D(3)多巴胺受体结合和mRNA水平大大降低。总之,这些发现提供了令人信服的证据,表明产后早期哺乳条件的破坏会导致中皮层皮质多巴胺神经元对压力和精神刺激药的反应发生深刻而持久的变化,并为个体在强迫性吸毒中的差异提供了神经生物学基础。

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