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Background: Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanoldrinking behavior in rats. Methods: We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb. Results: c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior. Conclusions: Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics. [ABSTRACT FROM AUTHOR]

Objective(s). Examine the effect of preoperative dose of IV ibuprofen on stress response and postoperative recovery in laparoscopic cholecystectomy patients. Design. Prospective, randomized, controlled, double-blind, multicenter trial. Setting. Three university-based, tertiary care hospitals. Subjects. Fifty-five adults, ASA 1, 2, or 3 scheduled for laparoscopic cholecystectomy were given a single preoperative dose of placebo or IV ibuprofen 800 mg. Methods. Neurobehavioral assessments were evaluated preoperatively, in PACU, POD 1, and POD 3, using the 40-item Quality of Recovery questionnaire (QoR40), 9-item Modified Fatigue Severity Scale (MFSS), and 15-item Geriatric Depression scale (GDS). Blood samples were taken for cytokines (TNF-alpha, IL-1β, IL-2, IL-6, IL-10, IFNγ), cortisol, CRP, epinephrine, and norepinephrine prior to the administration of study drug/placebo, intraoperatively, and after surgery. Results. Global QoR40 scores remained at baseline for ibuprofen patients but significantly decreased in the placebo group. Severity of fatigue increased in patients receiving placebo but had no change with ibuprofen. The placebo group had lower GDS scores on POD 3. Epinephrine and norepinephrine were significantly lower intraoperatively for the ibuprofen group. Cortisol decreased postoperatively in the ibuprofen group. There was an impact of drug treatment on the immune response, as seen by an increase in TNFαand an increase in IL-10 when compared with placebo. Conclusions. Our results suggest the addition of NSAIDs may improve the overall quality of recovery, postsurgical fatigue, and early postoperative outcomes. Preoperative administration of IV ibuprofen modulates the stress and inflammatory response, as demonstrated by a decrease in the level of cat-echolamines, cortisol, and cytokines. [ABSTRACT FROM AUTHOR]