Department of Psychiatry, Functional Neuroimaging Laboratory, Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Avenue, Baltimore, MD 21228-0247, USA.
Psychopharmacology (Berl). 2010 Mar;208(4):575-84. doi: 10.1007/s00213-009-1758-2.
The purpose of this study was to determine if acute nicotine attenuated ketamine-induced regional cerebral blood flow (rCBF).
Following 2-4 h of nicotine abstinence, healthy chronic smokers participated in four sets of rCBF studies, H2(15)O positron emission tomography, during a simple sensory motor control task. The four drug conditions studied were placebo, ketamine alone, nicotine alone, and ketamine + nicotine.
Intravenous ketamine increased rCBF in frontal, orbital-frontal, and anterior cingulate areas. Nicotine alone induced marked rCBF elevations in the lateral occipital cortex and rCBF suppressions in the basal ganglia and anterior cingulate cortex. Nicotine added to ketamine attenuated the ketamine-induced elevated rCBF in the anterior cingulate cortex but caused a marked rCBF increase in the orbital frontal region.
This study illustrates the interactive effects of ketamine, an NMDA receptor antagonist, and nicotine in multiple brain regions. Nicotine substantially ameliorated the effects of ketamine on anterior cingulate rCBF and, when given alone, markedly suppressed anterior cingulate rCBF. The enhanced, synergistic orbitofrontal effects observed with ketamine and nicotine together suggest a marked increase in excitatory neurotransmission in a brain region often linked to psychosis, reward, and addictive behaviors.
本研究旨在确定急性尼古丁是否能减弱氯胺酮引起的区域性脑血流（rCBF）。
在经历 2-4 小时的尼古丁戒断后，健康的慢性吸烟者参与了四项 rCBF 研究，使用 H2(15)O 正电子发射断层扫描，同时进行简单的感觉运动控制任务。研究中研究了四种药物条件：安慰剂、单独使用氯胺酮、单独使用尼古丁和氯胺酮+尼古丁。
静脉内给予氯胺酮可增加额叶、眶额和前扣带区域的 rCBF。单独使用尼古丁可引起外侧枕叶 rCBF 的显著升高，并抑制基底节和前扣带皮层的 rCBF。尼古丁与氯胺酮合用可减弱氯胺酮引起的前扣带皮层 rCBF 升高，但可引起眶额区域 rCBF 的显著升高。
本研究说明了 NMDA 受体拮抗剂氯胺酮和尼古丁在多个脑区的相互作用效应。尼古丁显著改善了氯胺酮对前扣带 rCBF 的作用，而单独使用时，尼古丁则明显抑制了前扣带 rCBF。氯胺酮和尼古丁合用观察到的增强的协同眶额效应提示兴奋性神经递质在与精神病、奖励和成瘾行为相关的脑区显著增加。
