This study examined the role of endocannabinoid signaling in stress-induced reinstatement of cocaine seeking and explored the interaction between noradrenergic and endocannabinergic systems in the process. A well-validated preclinical model for human relapse, the rodent conditioned place preference assay was used. Cocaine-induced place preference was established in C57BL/6 mice using injections of 15 mg/kg cocaine. Following extinction of preference for the cocaine-paired environment, reinstatement of place preference was determined following 6 min of swim stress, or cocaine injection (15 mg/kg, i.p.). The role of endocannabinoid signaling was studied using the cannabinoid antagonist AM-251 (3 mg/kg, i.p.). Another cohort of mice was tested for reinstatement following administration of the cannabinoid agonist CP 55,940 (10, 20 or 40 μg/kg, i.p.). The alpha-2 adrenergic antagonist BRL-44408 (5 mg/kg, i.p.) with or without CP 55,940 (20 μg/kg) was administered to a third group of mice. We found that: 1) AM-251 blocked forced swim-induced but not cocaine-induced reinstatement of cocaine-seeking behavior; 2) the cannabinoid agonist CP 55,940 did not reinstate cocaine-seeking behavior when administered alone but did synergize with a non-reinstating dose of the alpha-2 adrenergic antagonist BRL-44408 to cause reinstatement. These results are consistent with the hypothesis that stress exposure triggers the endogenous activation of CB1 receptors and that activation of the endocannabinoid system is required for the stress-induced relapse of the mice to cocaine seeking. Further, the data suggests that the endocannabinoid system interacts with noradrenergic mechanisms to influence stress-induced reinstatement of cocaine-seeking behavior.
Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.
The effects of methamphetamines (MAs) on trauma patient outcomes have been evaluated, but with discordant results. The purpose of this study was to identify hospital outcomes associated with MA use after traumatic injury. Retrospective review of adult trauma patients admitted to an American College of Surgeons verified–Level I trauma center who received a urine drug screen (UDS) between January 1, 2004 and December 31, 2013. Logistic regression analysis was used to identify factors associated with mortality. Patients with a negative UDS were used as controls. Among the 2321 patients included, 75.1 per cent were male, 81.9 per cent were white, and the average age was 39. Patients were grouped by UDS results (negative, MA only, other drug plus MA, or other drug without MA). A positive drug screen result of other drug without MA demonstrated a significantly lower risk for mortality, but longer intensive care unit and hospital length of stay, as well as increased ventilator days than negative results. Results of MA only did not alter the risk of mortality. These findings suggest that patients who test positive for MAs are not at an increased risk of in-hospital mortality when compared with patients having a negative drug screen.
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