• Ken Solt, Christa J Van Dort, Jessica J Chemali, Norman E Taylor, Jonathan D Kenny, and Emery N Brown.
• From the Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (K.S., C.J.V.D., and N.E.T.); Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital (J.J.C. and J.D.K.); and Department of Anaesthesia, Harvard Medical School; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts (E.N.B.).
• Anesthesiology. 2014 Aug 1;121(2):311-9.

BackgroundMethylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia.MethodsIn adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) or substantia nigra (n = 5). After a minimum 7-day recovery period, the isoflurane dose sufficient to maintain loss of righting was established. Electrical stimulation was initiated and increased in intensity every 3 min to a maximum of 120 µA. If stimulation restored the righting reflex, an additional experiment was performed at least 3 days later during continuous propofol anesthesia. Histological analysis was conducted to identify the location of the electrode tip. In separate experiments, stimulation was performed in the prone position during general anesthesia with isoflurane or propofol, and the electroencephalogram was recorded.ResultsTo maintain loss of righting, the dose of isoflurane was 0.9% ± 0.1 vol%, and the target plasma dose of propofol was 4.4 ± 1.1 µg/ml (mean ± SD). In all rats with VTA electrodes, electrical stimulation induced a graded arousal response including righting that increased with current intensity. VTA stimulation induced a shift in electroencephalogram peak power from δ (<4 Hz) to θ (4-8 Hz). In all rats with substantia nigra electrodes, stimulation did not elicit an arousal response or significant electroencephalogram changes.ConclusionsElectrical stimulation of the VTA, but not the substantia nigra, induces reanimation during general anesthesia with isoflurane or propofol. These results are consistent with the hypothesis that dopamine release by VTA neurons, but not substantia nigra neurons, induces reanimation from general anesthesia.

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