Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return.
Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return.
复制标题
DOI：
10.3390/biomedicines9091161
复制
发表时间：
2021-09-04
期刊：
影响因子：
4.7
通讯作者：
Cannizzaro C
中科院分区：
文献类型：
--
作者：
Brancato A;Castelli V;Lavanco G;Tringali G;Micale V;Kuchar M;D'Amico C;Pizzolanti G;Feo S;Cannizzaro C
青少年酗酒会影响伏隔核中支撑奖赏和应激处理的发育中的神经网络。本研究在大鼠中探究了青春期早期间歇性暴露于致醉酒精水平对以下方面的长期影响：（1）对自然积极刺激和不可逃避应激的反应；（2）应激轴功能；以及（3）伏隔核中的多巴胺能和谷氨酸能神经适应性。我们还评估了非致醉植物大麻素大麻二酚抵消（或逆转）酗酒样酒精暴露有害后果发展的潜在作用。我们的结果表明，青春期酗酒样酒精暴露会改变对积极刺激的敏感性，在早期和长期戒断期间产生社交和新奇触发的焦虑样行为以及被动应激应对方式。此外，在戒断期间，血清皮质酮以及下丘脑和伏隔核的促肾上腺皮质激素释放激素水平逐渐升高。此外，伏隔核酪氨酸羟化酶水平在戒断后期升高，而多巴胺转运体、D1和D2受体的表达在酗酒和戒断期间动态变化。再者，兴奋性突触后信号标记物——PSD95、Homer - 1和 - 2以及活性调节的脊柱形态蛋白Arc、LIM激酶1和FOXP1的表达在戒断后期增加。值得注意的是，在戒断期间给予亚慢性大麻二酚可减轻社交和新奇诱导的厌恶以及被动应激应对，并纠正高反应性应激轴以及伏隔核中与多巴胺和谷氨酸相关的神经可塑性。总体而言，青春期大鼠暴露于酗酒样酒精水平会使伏隔核在戒断期间由于神经可塑性和应激轴内稳态的扰动而成为薄弱环节。大麻二酚在提高对酗酒样酒精有害影响的行为、神经内分泌和分子抗性方面具有良好的潜力。
Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress; (2) stress-axis functionality; and (3) dopaminergic and glutamatergic neuroadaptation in the NAc. We also assess the potential effects of the non-intoxicating phytocannabinoid cannabidiol, to counteract (or reverse) the development of detrimental consequences of binge-like alcohol exposure. Our results show that adolescent binge-like alcohol exposure alters the sensitivity to positive stimuli, exerts social and novelty-triggered anxiety-like behaviour, and passive stress-coping during early and prolonged withdrawal. In addition, serum corticosterone and hypothalamic and NAc corticotropin-releasing hormone levels progressively increase during withdrawal. Besides, NAc tyrosine hydroxylase levels increase at late withdrawal, while the expression of dopamine transporter, D1 and D2 receptors is dynamically altered during binge and withdrawal. Furthermore, the expression of markers of excitatory postsynaptic signaling—PSD95; Homer-1 and -2 and the activity-regulated spine-morphing proteins Arc, LIM Kinase 1 and FOXP1—increase at late withdrawal. Notably, subchronic cannabidiol, during withdrawal, attenuates social- and novelty-induced aversion and passive stress-coping and rectifies the hyper-responsive stress axis and NAc dopamine and glutamate-related neuroplasticity. Overall, the exposure to binge-like alcohol levels in adolescent rats makes the NAc, during withdrawal, a locus minoris resistentiae as a result of perturbations in neuroplasticity and in stress-axis homeostasis. Cannabidiol holds a promising potential for increasing behavioural, neuroendocrine and molecular resilience against binge-like alcohol harmful effects.
登录
查看更多内容
与奖励相关行为中的多巴胺信号传导。
影响因子：
3.5
作者：
Baik JH
通讯作者：
Baik JH
影响因子：
5.3
作者：
Butts, Andrew R.;Ojelade, Shamsideen;Rothenfluh, Adrian
通讯作者：
Rothenfluh, Adrian
影响因子：
9.3
作者：
Di Bartolomeo, Martina;Stark, Tibor;Micale, Vincenzo
通讯作者：
Micale, Vincenzo
影响因子：
3.4
作者：
Cryan, JF;Page, ME;Lucki, I
通讯作者：
Lucki, I
影响因子：
2.9
作者：
BRODIE, MS;SHEFNER, SA;DUNWIDDIE, TV
通讯作者：
DUNWIDDIE, TV