Immunoreactivity and distribution of Fos in the mouse brain following diverse general anesthetics.

General anesthesia induces a range of effects, including unconsciousness, analgesia, amnesia, and immobility. Despite its widespread use for over a century, the underlying mechanisms remain incompletely understood. This study aims to investigate whether different intravenous anesthetics share common neuronal targets. Propofol (180 mg/kg), midazolam (75 mg/kg), and esketamine (250 mg/kg) were intraperitoneally injected in C57BL/6J mice, respectively. After one hour of anesthesia, mice were transcardially perfused, and their brains were examined for Fos protein localization to assess changes in neuronal activity across the central nervous system. The 14 selected regions of interest (ROIs) associated with sleep-wake regulation, emotional stress processing, or pain modulation include: oval division of the bed nucleus of the stria terminalis (ovBNST), basal forebrain (BF), ventrolateral preoptic nucleus (VLPO), paraventricular hypothalamic nucleus (PvH), supraoptic nucleus (SON), central amygdaloid nucleus (CeA), paraventricular thalamic nucleus (PVT), lateral habenular nucleus (LHb), tuberomammillary nucleus (TMN), Edinger-Westphal nucleus (EW), dorsal raphe nucleus (DR), ventrolateral periaqueductal gray (vlPAG), locus coeruleus (LC) and parabrachial nucleus (PB). Following the administration of three different anesthetics, the immunoreactivity of Fos in the 14 ROIs increased in the following brain regions: ovBNST, LHb, PvH, SON, CeA, and EW; however, the BF, PVT, DR, LC, and PB showed no appreciable changes, while the VLPO, TMN, and vlPAG exhibited variable Fos immunoreactivity across the three anesthetic groups. These findings suggest that propofol, midazolam, and esketamine may commonly enhance neuronal activity in specific brain regions, providing new morphological insights into the mechanisms of general anesthesia.