Kohut Stephen J, Mintzopoulos Dionyssios, Kangas Brian D, Shields Hannah, Brown Kelly, Gillis Timothy E, Rohan Michael L, Bergman Jack, Kaufman Marc J
Behavioral Biology Program, McLean Hospital, Belmont, MA, 02478, USA.
McLean Imaging Center, McLean Hospital, Belmont, MA, 02478, USA.
Transl Psychiatry. 2020 Dec 2;10(1):420. doi: 10.1038/s41398-020-01101-z.
Long-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen-two brain regions involved in cognitive function and motoric behavior-identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299-424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.
长期使用可卡因与多种影响日常功能的神经和行为缺陷有关。本研究旨在通过全脑分析，检验慢性可卡因自我给药对背侧前扣带回（dACC）和壳核静息态功能连接的影响，这两个脑区参与认知功能和运动行为。六只成年雄性松鼠猴在140次实验中自我给药可卡因（0.32毫克/千克/注射）。另外六只约1.5年未接受任何药物治疗的猴子作为无药物对照组。在异氟烷麻醉下进行9.4特斯拉的静息态功能磁共振成像实验。使用置于左侧dACC或壳核的种子区域得出功能连接图。结果显示，可卡因的自我给药行为稳定，平均总摄入量为367毫克/千克（范围：299 - 424毫克/千克）。在可卡因组中，dACC种子与主要参与运动行为的区域之间的功能连接较弱，而dACC种子与涉及奖励和认知加工的区域之间的连接较强。在壳核种子区域，壳核与其他运动区域以及调节高级执行功能的前额叶区域之间的广泛连接较弱；与奖励相关区域的连接较强。dACC连接性与可卡因总摄入量相关。这些数据表明，近期有可卡因自我给药史的受试者与对照组相比，参与运动、奖励和认知加工的区域之间的功能连接存在差异；在dACC中，连接性似乎与慢性暴露期间的可卡因累积剂量有关。
