The trace amine associated receptor (TAAR) 1 is a new G protein coupled receptor that critically modulates central dopaminergic system. Recently, several selective TAAR1 ligands have been described to possess antipsychotic and antidepressant-like activities. However, it is unknown of the role of these ligands in modulating psychostimulant-induced neurobehavioral plasticity. This study examined the effects of a selective TAAR1 agonist, RO5263397, on cocaine induced behavioral sensitization in rats, a rodent model of drug-induced behavioral plasticity. Daily treatment with 15 mg/kg cocaine (i.p., 7 days) induced robust locomotor sensitization in rats. RO5263397 (1–10 mg/kg, i.p.) alone did not significantly alter the locomotor activity. Acute treatment with RO5263397 (3.2 and 10 mg/kg) did not significantly modify cocaine-induced hyperactivity; however, the induction of locomotor sensitization was significantly blocked after 7 days of daily RO5263397 treatment. More importantly, the expression of locomotor sensitization remained significantly attenuated when rats were re-tested 7 days after the last drug treatment. The marked attenuation of cocaine sensitization was also evidenced by the suppression of the dose-effect function (3.2 – 32 mg/kg) of cocaine sensitization. Together, these data represent the first to report a critical modulatory role of TAAR 1 agonists in cocaine-induced behavioral plasticity, which may be indicative of its potential role for altering other long-lasting behavioral maladaptations of cocaine including drug addiction.

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Background Studies on the epidemiology of sepsis in intensive care units (ICUs) of prefecture-level hospitals in China are rare. This study aimed to investigate the epidemiological characteristics and mortality risk factors of sepsis in ICUs of tertiary hospitals in Sichuan, China. Material/Methods In this prospective, multicenter, observational study, patients admitted to the ICU of 7 tertiary hospitals in Sichuan (China) between October 10, 2017 and January 9, 2018 were screened for sepsis using the Sepsis-3 criteria. Patients with sepsis were included. Results Of the 1604 patients screened for sepsis, 294 (18.3%) had sepsis, and 140 (47.6%) had septic shock. Of these, 169 (57.5%) died. Multivariable analysis showed that central nervous system dysfunction (odds ratio [OR]=2.59, 95% confidence interval [CI]: 1.15–5.84, P=0.022), lowest blood phosphorus level (OR=2.56, 95% CI: 1.21–5.44, P=0.014), highest lactate level (OR=1.20, 95% CI: 1.10–1.32, P<0.001), 24-h Acute Physiologic Assessment and Chronic Health Evaluation-II (APACHE-II) score (OR=1.08, 95% CI: 1.03–1.13, P=0.002), and lung infection (OR=2.57, 95% CI: 1.30–5.09, P=0.007) were independently associated with mortality in patients with sepsis. Conclusions The prevalence and mortality rates of sepsis are high in tertiary hospital ICUs in Sichuan, China. The APACHE-II score on day 1 after diagnosis, acute central nervous system dysfunction, lowest blood phosphorus, high serum lactate, and lung infection were independent risk factors of mortality in patients with sepsis.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARδ and the activity of SMS. In his study, macrophage-induced foam cells were utilized to model important pathological changes that occur in AS. The influence of PPARδ agonism by GW501516 on SMS and its product molecule SM were measured. Results indicated that the activation of PPARδ was correlated in a positive manner with the activity of SMS2, and the content of SM was dose dependently increased by GW501516. Together, this study represents the first to suggest that PPARδ activation may be a potential risk of AS through enhancing activity of SMS2.