The mechanisms of anesthetic abuse

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I have investigated the effects of various anesthetics on dopamine release in the rat nucleus accumbens(Ncs), which is closely related to drug addiction and psychotomimetic activity of drugs, and c-Fos expression in the rat posterior cingulate and retrosplenial cortices(PC/RS), which are considered to represent psychotomimetic activity of NMDA receptor antagonists. I have also studied the effects of several intravenous anesthetics on sigma 1 receptors, which have various CNS effects including drug addiction.Ketamine and nitrous oxide increased dopamine release in the Nac but xenon tended to decrease it. Repetitive administration of ketamine and nitrous oxide for 5 days did not further increase the dopamine release. Pentobarbital decreased the dopamine release and inhibited the ketamine-induced increase in dopamine release. Ketamine and nitrous oxide induced marked c-Fos expression in the PC/RS but xenon did not induce it. Nitrous oxide augmented the ketamine-induced c-Fos expression but xenon inhibited it. Clinically relevant doses of propofol affected sigma 1 receptor by a receptor binding assay, indicating that various CNS effects, such as drug addiction, psychotic activity, neuroprotection and anti-emetic activity, by propofol may be mediated, at least partly, by sigma 1 receptors.