ABSTRACT
BACKGROUND: Ethanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways. METHODS: Male Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays. RESULTS: MESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS. CONCLUSIONS: These results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.
Subject(s)
Anti-Anxiety Agents/administration & dosage , Anxiety/drug therapy , Central Amygdaloid Nucleus/drug effects , Ethanol/adverse effects , Neuropeptides/metabolism , Substance Withdrawal Syndrome/complications , Ziziphus/chemistry , Animals , Anxiety/etiology , Anxiety/genetics , Anxiety/metabolism , Central Amygdaloid Nucleus/metabolism , Corticotropin-Releasing Hormone/metabolism , Humans , Male , Rats , Rats, Sprague-Dawley , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Corticotropin-Releasing Hormone/metabolismABSTRACT
OBJECTIVE: We performed the present meta-analysis in order to evaluate the influence of a common polymorphism (C825T, rs5443 C>T) in the GNB3 gene on the efficacy of antidepressants in the treatment of major depressive disorder (MDD). METHOD: A relevant literature was searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, Texas USA) was used for this meta-analysis. Odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were calculated. RESULTS: Our findings suggested that the GNB3 C825T polymorphism was significantly correlated with a higher response rate to antidepressants in MDD patients under the allele and dominant models. Furthermore, we found significant associations between GNB3 C825T polymorphisms and antidepressant-induced remission in MDD patients. Ethnicity-stratified analysis indicated that GNB3 C825T polymorphisms may be strongly related to the efficacy of antidepressants in the treatment of MDD among Asians, but not in Caucasians (all P>0.05). CONCLUSION: Our findings provide empirical evidence that GNB3 C825T polymorphisms may be correlated with the efficacy of antidepressants in the treatment of MDD, especially among Asians patients.