Enhanced neuronal and blunted hemodynamic reactivity to cocaine in the prefrontal cortex following extended cocaine access: optical imaging study in anesthetized rats.
Enhanced neuronal and blunted hemodynamic reactivity to cocaine in the prefrontal cortex following extended cocaine access: optical imaging study in anesthetized rats.
复制标题
DOI：
10.1111/adb.12615
复制
发表时间：
2019-05
影响因子：
3.4
通讯作者：
Du C
中科院分区：
文献类型：
--
作者：
Allen CP;Park K;Li A;Volkow ND;Koob GF;Pan Y;Hu XT;Du C
可卡因成瘾与前额叶皮层（PFC）功能障碍有关，这有助于复发和强迫性吸毒。为了评估可卡因对神经元和血管活性的影响是否会导致PFC功能障碍，我们使用光学相干断层扫描（OCT）和多波长激光散斑（MW-LSI）来测量血管化和血流动力学，并使用GCaMP 6 f来监测细胞内Ca 2+水平（[Ca 2 +]in）作为神经元活性的标志物。给予大鼠短时间（1小时; ShA）或长时间（6小时; LgA）的可卡因自我给药。正如预期的那样，LGA而不是ShA大鼠增加了可卡因摄入量。在未经处理的大鼠中，急性可卡因降低了氧合血红蛋白，增加了脱氧血红蛋白，并减少了PFC中的脑血流量，这可能是由于可卡因诱导的血管收缩。ShA大鼠表现出增强的血流动力学反应和较慢的恢复可卡因后，与天真的。LgA大鼠表现出钝的血流动力学反应，但增强PFC神经元[Ca 2 +]的增加后，可卡因的挑战与药物摄入。ShA和LgA组的血管密度较高，表明血管生成，可能是为了补偿可卡因的血管收缩作用。皮质醇自身给药改变了PFC脑血管反应，在ShA中增强，在LgA动物中减弱。相反，LgA而不是ShA动物在PFC中对急性可卡因表现出致敏神经元反应性。（减少）和神经元反应在LgA大鼠中（增强）表明这些构成了不同的影响，这表明神经元效应而不是血管效应与成瘾中可卡因摄入量的增加有关，而其在PFC中的血管效应可能导致认知缺陷增加，容易复发
Cocaine addiction is associated with dysfunction of the prefrontal cortex (PFC), which facilitates relapse and compulsive drug taking. To assess if cocaine’s effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography (OCT) and multiwavelength laser speckle (MW-LSI) to measure vascularization and hemodynamics, and used GCaMP6f to monitor intracellular Ca2+ levels ([Ca2+]in) as a marker of neuronal activity. Rats were given short (1hr; ShA) or long (6hr; LgA) access cocaine self-administration. As expected, LgA but not ShA rats escalated cocaine intake. In naïve rats, acute cocaine decreased oxygenated hemoglobin, increased deoxygenated hemoglobin, and reduced cerebral blood flow in PFC, likely due to cocaine-induced vasoconstriction. ShA rats showed enhanced hemodynamic response and slower recovery after cocaine, versus naïve. LgA rats showed a blunted hemodynamic response, but an enhanced PFC neuronal [Ca2+]in increase after cocaine challenge associated with drug intake. Both ShA and LgA groups had higher vessel density, indicative of angiogenesis, presumably to compensate for cocaine’s vasoconstricting effects. Cocaine self-administration modified the PFC cerebrovascular responses enhancing it in ShA and attenuating it in LgA animals. In contrast, LgA but not ShA animals showed sensitized neuronal reactivity to acute cocaine in the PFC. The opposite changes in hemodynamics (decreased) and neuronal responses (enhanced) in LgA rats indicate that these constitute distinct effects, and suggest that the neuronal and not the vascular effects are associated with escalation of cocaine intake in addiction whereas its vascular effect in PFC might contribute to cognitive deficits that increase vulnerability to relapse.
登录
查看更多内容
DOI：
10.1098/rstb.2008.0106
发表时间：
2008-10-12
影响因子：
6.3
作者：
Garavan, Hugh;Kaufman, Jacqueline N.;Hester, Robert
通讯作者：
Hester, Robert
影响因子：
5.7
作者：
Lu, Hanbing;Chefer, Svetlana;Kurup, Pradeep K.;Guillem, Karine;Vaupel, D. Bruce;Ross, Thomas J.;Moore, Anna;Yang, Yihong;Peoples, Laura L.;Stein, Elliot A.
通讯作者：
Stein, Elliot A.
DOI：
10.1109/jstqe.2015.2503319
发表时间：
2016-07-01
影响因子：
4.9
作者：
Chen, Wei;Park, Kicheon;Du, Congwu
通讯作者：
Du, Congwu
影响因子：
10.6
作者：
Franklin, TR;Acton, PD;Childress, AR
通讯作者：
Childress, AR
影响因子：
2.3
作者：
Byas-Smith, MG;Li, J;Denson, DD
通讯作者：
Denson, DD