Toluene Inhalation Causes Early Anxiety and Delayed Depression with Regulation of Dopamine Turnover, 5-HT1A Receptor, and Adult Neurogenesis in Mice

Inhaled solvents such as toluene are of particular concern due to their abuse potential that is easily exposed to the environment. The inhalation of toluene causes various behavioral problems, but, the effect of short-term exposure of toluene on changes in emotional behaviors over time after exposure and the accompanying pathological characteristics have not been fully identified. Here, we evaluated the behavioral and neurochemical changes observed over time in mice that inhaled toluene. The mice were exposed to toluene for 30 min at a concentration of either 500 or 2,000 ppm. Toluene did not cause social or motor dysfunction in mice. However, increased anxiety-like behavior was detected in the short-term after exposure, and depression-like behavior appeared as delayed effects. The amount of striatal dopamine metabolites was significantly decreased by toluene, which continued to be seen for up to almost two weeks after inhalation. Additionally, an upregulation of serotonin 1A (5-HT1A) receptor in the hippocampus and the substantia nigra, as well as reduced immunoreactivity of neurogenesis markers in the dentate gyrus, was observed in the mice after two weeks. These results suggest that toluene inhalation, even single exposure, mimics early anxietyand delayed depression-like emotional disturbances, underpinned by pathological changes in the brain.

Laxative effect of peanut sprout extract

Certain phenolic compounds are known to exhibit laxative properties. Seed sprouts, such as those of peanut, are known to promote de novo biosynthesis of phenolic compounds. This study was conducted to examine the potential laxative properties of 80% (v/v) ethanolic extract of peanut sprout (PSE), which contains a high concentration of phenolic compounds such as resveratrol. For this, SD rats were orally administered PSE while a control group was incubated with saline. Laxative effects were examined in both groups of rats. Constipation induced by loperamide in SD rats was improved by administration of PSE. Constipated rats showed increased intestinal movement of BaSO4 upon administration of PSE compared to the control, and the groups administered 100 or 1,000 mg PSE/kg bw were not significantly different in transit time of the indicator. However, colon length was not statistically different among the experimental groups, although it was longer in the group incubated with 1 g PSE/kg bw compared to other groups. Further, there was no significant difference in stool number among the experimental groups. Taken together, these findings show that PSE has a laxative effect in a rat model of loperamide-induced constipation.

The Change of nicotine and cotinine concentrations in the saliva of participants in the Quit-Smoking Clinic in Daejeon / 대한구강보건학회지

OBJECTIVES: The Korea Health Promotion Foundation has performed the None-Smoking Project using the Quit-Smoking Clinics in all health care centers. The success rate of quitting smoking in the Quit-Smoking Clinics have run over 40% in the self-reports. The aim of this study was to assess the success rate of quitting smoking using the nicotine and cotinine concentrations in saliva and to find out the factors that influence the success of quitting smoking. METHODS: The author collected the data of 122 participants from the Quit-Smoking Clinic in the city of Daejeon and the data 13 nonsmokers as control after their written consent in 2009-2010. Following the initial visit, the unstimulated saliva samples were collcted at the visits after 2 weeks, 2 months, 4 months and 6. The concentrations of nicotine, cotinine, and OH-cotinine were analyzed using the High Performance Liquid Chromatography. The cutoff for the cotinine concentration that distinguished the smokers from nonsmokers was set at 10 ng/ml. RESULTS: The baseline participants who visited the clinic were 84 paritcipants after 2 weeks, 65 after 2 months, 40 after 4 months, and 22 after 6 months. The median concentrations of cotinine (P=0.017) and OH-cotinine (P0.7). The amount of smoking in a day, the period of smoking, and the total amount of smoking did not correlate to the success of quitting smoking as measured in the cotinine level. CONCLUSIONS: In spite of the limitation of the high drop out rate in the participants, it was suggested that the active intervention at 2 weeks could make the success rate of quitting smoking higher, as the cotinine level at 2 weeks correlated to the concentrations after that point very positively.

The Effect of CYP2D6/3A5 Genotypes on Plasma Concentrations of Haloperidol after Adjunctive Treatment of Aripiprazole

OBJECTIVES: To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. METHOD: Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. *1, *5, and *10 B alleles of CYP2D6 and *1 and *3 alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05. RESULTS: In the frequency of CYP2D6 genotype, *1/*10 B type was most frequent (36.5%) and *1/*1 (30.8%), *10B/*10B (17.3%) types followed. In the frequency of CYP3A5 genotype, *3/*3 type was found in 63.5% of subjects, and *1/*3 type and *1/*1 were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol. CONCLUSION: No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

Inhibitory effect of Suaeda asparagoides (Miq.) extract on the motility of rat gastric antrum is mediated by beta-adrenoceptor / 한국실험동물학회지

Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 microg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 microM), N omega-Nitro-L-arginine methyl ester hydrochloride (100 microM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 microM), ryanodine (10 microM) and phentolamine (10 microM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 microM). Furthermore, the beta-adrenergic receptor antagonist, propranolol (10 microM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via a-adrenergic receptors and sarcoplasmic reticulum Ca2+ ATPase.