Limbic system participates in mediating the effects of general anesthetics

In a previous study, we reported that inactivation of the medial septum or the hippocampus by muscimol, a GABA(A) receptor agonist, potentiated the effects of a general anesthetic. In this study, we further investigated whether other structures that are connected to the septohippocampal system are involved in mediating general anesthesia. In freely behaving rats, muscimol (0.25 mg) or saline was infused intracerebrally into one of four areas - the supramammillary area (SUM), nucleus accumbens (NAC), ventral pallidum (VP), and ventral tegmental area (VTA) - and righting, pain, and EEG responses were recorded following either halothane or sodium pentobarbital, representing inhalational and injectable general anesthetic, respectively. The effect of halothane (2%) or pentobarbital (20 mg/kg i.p.) in abolishing the righting, pain response, or low-voltage neocortical activity was enhanced, and the initial behavioral hyperactivity (delirium) was reduced, after muscimol as compared to after saline infusion in SUM, NAC, VP, and VTA. EEGs in the hippocampus and the sensorimotor cortex following halothane or pentobarbital showed increased delta, and decreased hippocampal theta and gamma waves after muscimol infusion as compared to saline infusion in SUM, NAC, VP, and VTA. By contrast, infusion of muscimol in the median raphe increased locomotion and did not significantly alter the behavioral or EEG effects of halothane or pentobarbital. It is suggested that structures that activate the limbic cortices (MS, SUM, and VTA but not the median raphe) or mediate the output of the hippocampus (NAC and VP) normally participate in maintaining consciousness and inactivation of these structures potentiates the response to a general anesthetic.