Abstinence to chronic methamphetamine switches connectivity between striatal, hippocampal and sensorimotor regions and increases cerebral blood volume response.
Abstinence to chronic methamphetamine switches connectivity between striatal, hippocampal and sensorimotor regions and increases cerebral blood volume response.
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DOI：
10.1016/j.neuroimage.2018.02.059
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发表时间：
2018-07-01
期刊：
影响因子：
5.7
通讯作者：
Jenkins BG
中科院分区：
文献类型：
--
作者：
Choi JK;Lim G;Chen YI;Jenkins BG
甲基苯丙胺（冰毒）和可卡因等其他精神兴奋剂是社会的一个长期问题，长期使用者极易复发。我们表明，在一个慢性甲基苯丙胺管理模型，停药超过一周产生更大的变化，在整体甲基诱导的脑连接和脑血容量（CBV）的反应比发生变化后立即甲基管理。显示最大变化的区域是海马、边缘纹状体和感觉运动皮质区域以及脑干区域，包括脚桥被盖（PPTg）和桥核--已知这些区域在介导戒断后恢复吸毒方面很重要。这些变化伴随着行为敏化发生，并且似乎通过多巴胺D1和D3的增加以及D2受体蛋白和mRNA表达的减少来介导。我们进一步确定了一个新的区域的背侧尾状核/壳核，与低密度的钙结合蛋白神经元，具有相反的血流动力学反应，甲基比其余的尾状核/壳核和海马，并显示出非常强的相关性与背侧CA 1和CA 3海马。这种相关性在冰毒戒断后从CA 1/CA 3切换到与腹侧海马（腹侧下托）和延髓核的强连接。这些数据为大脑连接的时间改变提供了新的证据，其中慢性冰毒可以从认知控制区域到介导药物恢复的区域破坏海马-纹状体相互作用。我们的研究结果还表明，在用甲基或D3偏好激动剂挑战后诱导的CBV变化的迹象和幅度是使用蛋白质或mRNA水平在D1，D2和D3受体中发生的相对变化的互补读数。
Methamphetamine (meth), and other psychostimulants such as cocaine, present a persistent problem for society with chronic users being highly prone to relapse. We show, in a chronic methamphetamine administration model, that discontinuation of drug for more than a week produces much larger changes in overall meth-induced brain connectivity and cerebral blood volume (CBV) response than changes that occur immediately following meth administration. Areas showing the largest changes were hippocampal, limbic striatum and sensorimotor cortical regions as well as brain stem areas including the pedunculopontine tegmentum (PPTg) and pontine nuclei – regions known to be important in mediating reinstatement of drug-taking after abstinence. These changes occur concomitantly with behavioral sensitization and appear to be mediated through increases in dopamine D1 and D3 and decreases in D2 receptor protein and mRNA expression. We further identify a novel region of dorsal caudate/putamen, with a low density of calbindin neurons, that has an opposite hemodynamic response to meth than the rest of the caudate/putamen and accumbens and shows very strong correlation with dorsal CA1 and CA3 hippocampus. This correlation switches following meth abstinence from CA1/CA3 to strong connections with ventral hippocampus (ventral subiculum) and nucleus accumbens. These data provide novel evidence for temporal alterations in brain connectivity where chronic meth can subvert hippocampal – striatal interactions from cognitive control regions to regions that mediate drug reinstatement. Our results also demonstrate that the signs and magnitudes of the induced CBV changes following challenge with meth or a D3-preferring agonist are a complementary read out of the relative changes that occur in D1, D2 and D3 receptors using protein or mRNA levels.
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影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
7.6
作者：
Andreoli, M;Tessari, M;Heidbreder, CA
通讯作者：
Heidbreder, CA
影响因子：
1.9
作者：
Cho, JW;Sharp, PE
通讯作者：
Sharp, PE
影响因子：
5
作者：
Davidson, Colin;Gopalan, Rupa;Ellinwood, Everett H.
通讯作者：
Ellinwood, Everett H.
在使用甲基苯丙胺治疗后复发的时间：对模式和预测因子的长期观点。
影响因子：
4.2
作者：
Brecht ML;Herbeck D
通讯作者：
Herbeck D