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Transient receptor potential vanilloid type 1 (TRPV1), a nonselective cation channel, is a well-known pain-related receptor. TRPV1 involvement in morphine-induced antinociception, tolerance, and withdrawal symptoms has been previously reported. Emerging evidence indicates that TRPV1 may be related to both the cellular and behavioral effects of addictive drugs. In the present study, we investigated the role of TRPV1 in morphine reward using the conditioned place preference (CPP) paradigm in mice. Repeated morphine treatments upregulated TRPV1 expression in the dorsal striatum (DSt). Treatment with a TRPV1 agonist potentiated morphine reward, and pretreatment with TRPV1 antagonists attenuated these effects. Microinjection of a selective TRPV1 antagonist into the DSt significantly inhibited morphine-CPP. In addition, treatment with a TRPV1 antagonist suppressed morphine-induced increases in m-opioid receptor binding, adenylyl cyclase 1 (AC1), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa B (NF-kB) expression in the DSt. Administering a p38 inhibitor not only prevented morphine-CPP, but also prevented morphine-induced NF-kB and TRPV1 activation in the DSt. Furthermore, injecting an NF-kB inhibitor significantly blocked morphine-CPP. Our findings suggest that TRPV1 in the DSt contribute to morphine reward via AC1, p38 MAPK, and NF-kB. Brain TRPV1 may serve as a novel therapeutic target to treat morphine-addictive disorders.

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.

The androgen receptor (AR) is increasingly considered as a potential biomarker for breast cancer. Nevertheless, the prognostic value of AR expression in patients with triple negative breast cancer (TNBC) remains controversial. Therefore, in this meta-analysis, we investigated AR expression and its impact on survival outcome. PubMed, Embase, the Cochrane Library, and references of articles were searched to identify relevant studies that investigated the association between AR expression and prognosis in patients diagnosed with TNBC and were published between 1946 and May 2019. The hazard ratio (HR) and confidence interval (CI) of disease-free survival, overall survival, distant disease-free survival, and recurrence-free survival were weighted and pooled by using the fixed-effect or randomeffect model based on the heterogeneity of included studies. A total of 27 studies including 4914 patients with TNBC were included. AR was expressed in 27.96% (1315/4703) of patients with TNBC. In addition, AR expression in TNBC was not associated with disease-free survival (HR, 0.923; 95% CI, 0.671-1.271; P ¼ .634), overall survival (HR, 0.910; 95% CI, 0.678-1.222; P ¼ .531), distant disease-free survival (HR, 1.02; 95% CI, 0.96-1.08; P ¼ .489), or recurrence-free survival (HR, 0.957; 95% CI, 0.462-1.982; P ¼ .906) in TNBC, regardless of confounding factors and heterogeneity that existed among included studies. In patients with TNBC, AR expression is not associated with prognosis.

Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.

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