The interactive effects of ketamine and nicotine on human cerebral blood flow

Aim: The purpose of this study was to determine if acute nicotine attenuated ketamine-induced regional cerebral blood flow (rCBF). Method: Following 2-4 h of nicotine abstinence, healthy chronic smokers participated in four sets of rCBF studies, H ₂ 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. Results: 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. Conclusion: 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.