Acute Effects of Typical and Atypical Antipsychotic Drugs on the Release of Dopamine from Prefrontal Cortex, Nucleus Accumbens, and Striatum of the Rat: An In Vivo Microdialysis Study

In vivo microdialysis has been used to study the acute effects of antipsychotic drugs on the extracellular level of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. (-)-Sulpiride (20, 50, and 100 mg/kg i.v.) and haloperidol (0.1 and 0.5 mg/kg i.v.) enhanced the outflow of dopamine in the striatum and nucleus accumbens. In the medial prefrontal cortex, (-)-sulpiride at all doses tested did not significantly affect the extracellular level of dopamine. The effect of haloperidol was also attenuated in the medial prefrontal cortex; 0.1 mg/kg did not increase the outflow of dopamine and the effect of 0.5 mg/kg haloperidol was of shorter duration in the prefrontal cortex than that observed in striatum and nucleus accumbens. The atypical antipsychotic drug clozapine (5 and 10 mg/kg) increased the extracellular concentration of dopamine in all three regions. In contrast to the effects of sulpiride and haloperidol, that of clozapine in the medial prefrontal cortex was profound. These data suggest that different classes of antipsychotic drugs may have distinct effects on the release of dopamine from the nigrostriatal, mesolimbic, and mesocortical terminals.     

Excitatory Amino Acid Receptors in the Ventral Tegmental Area Regulate Dopamine Release in the Ventral Striatum

Abstract: The role of excitatory amino acid (EAA) receptors located in the ventral tegmental area (VTA) in tonic and phasic regulation of dopamine release in the ventral striatum was investigated. Microdialysis in conscious rats was used to assess dopamine release primarily from the nucleus accumbens shell region of the ventral striatum while applying EAA antagonists or agonists to the VTA. Infusion of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (25 and 100 µ M ) into the VTA did not affect dopamine release in the ventral striatum. In contrast, intra-VTA infusion of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (100 and 500 µ M ) dose-dependently decreased the striatal release of dopamine. Intra-VTA application of the ionotropic EAA receptor agonists NMDA and AMPA dose-dependently (10 and 100 µ M ) increased dopamine efflux in the ventral striatum. However, infusion of 50 or 500 µ M trans -(±)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), a metabotropic EAA receptor agonist, did not significantly affect these levels. These data suggest that NMDA receptors in the VTA exert a tonic excitatory influence on dopamine release in the ventral striatum. Furthermore, dopamine neurotransmission in this region may be enhanced by activation of NMDA and AMPA receptors, but not ACPD-sensitive metabotropic receptors, located in the VTA. These data further suggest that EAA regulation of dopamine release primarily occurs in the VTA as opposed to presynaptically at the terminal level.     

Epidemics of Rhizoctonia Root Rot in Association with Biological and Physicochemical Properties of Field Soil in Bean Crops

During two growing seasons (2008 and 2009), the associations of Rhizoctonia root rot (RRR) with a number of soil properties were determined at different growth stages in 122 commercial bean fields in Zanjan, Iran. Mean RRR incidence at a level of 4–25% sand content was lower than that at 45–65% level. Damage by fly puparia had no significant effect on RRR incidence and occurrence. A greater RRR incidence was detected in field soils treated with fungicides compared with non‐treated soils. A lower RRR incidence was associated with the highest level of soil organic matter (1.2–1.8) compared with the lowest level, 0.4–0.8. The highest RRR incidence corresponded with no rhizobial nodulation compared with highly nodulated bean roots. RRR incidence was negatively correlated with soil silt and organic matter content at R6–7 and R9 growth stages. RRR‐affected fields were recognized with a greater soil pH (V3) and sand content (R9), and a lower silt (R9) and organic matter content (R6–7 and R9) in comparison with RRR‐free fields. Loadings and linear regressions between RRR incidence and principal component scores indicated that the most effective soil characteristic linked to the disease was silt at V3, sand at R6–7 and organic matter at R9 stage. This new epidemiological information extends our knowledge of the bean–RRR–soil interaction on a regional basis.     

Thermodynamic and spectroscopic investigations of TMPyP4 association with guanine- and cytosine-rich DNA and RNA repeats of C9orf72

Background

An expansion of the hexanucleotide repeat (GGGGCC)n·(GGCCCC)n in the C9orf72 promoter has been shown to be the cause of Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The C9orf72 repeat can form four-stranded structures; the cationic porphyrin (TMPyP4) binds and distorts these structures.

Stress-induced acidification may contribute to formation of unusual structures in C9orf72-repeats

Background

Expansion of the C9orf72 hexanucleotide repeat (GGGGCC)_n·(GGCCCC)_n is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both strands of the C9orf72 repeat have been shown to form unusual DNA and RNA structures that are thought to be involved in mutagenesis and/or pathogenesis. We previously showed that the C-rich DNA strands from the C9orf72 repeat can form four-stranded quadruplexes at neutral pH. The cytosine residues become protonated under slightly acidic pH (pH?4.5–6.2), facilitating the formation of intercalated i-motif structures.

Gene polymorphisms of macrophage migration inhibitory factor affect susceptibility to chronic hepatitis B virus infection in an Iranian cohort

Macrophage migration inhibitory factor (MIF), a key proinflammatory mediator, plays important roles in chronic diseases. In this study, an attempt was made to clarify the associations between some functional polymorphisms such as MIF‐173 G/C, MIF 95 bp and 189 bp insertion/deletion (I/D) polymorphisms and chronic hepatitis B virus (HBV) infection. Polymorphisms were assessed in 221 HBV patients and 200 normal subjects. MIF‐173 G/C and MIF 95 bp and 189 bp I/D polymorphisms were genotyped using PCR–RFLP and PCR, respectively. When allele and genotype frequencies of the variants were compared between patients and controls by the χ² test, it was found that the frequency of MIF‐173 G/C genotypes differed significantly between patients with chronic HBV and healthy controls (P < 0.05). Carriers of the MIF ‐173‐C allele were at significantly higher risk of HBV infection than carriers of the MIF ‐173‐G allele (P = 0.009, OR = 1.549, 95% CI = 1.114 ? 2.155). Moreover, 95 bp I/D polymorphism was not associated with CP and the 185 bp I/D variant was not polymorphic in our group of subjects. The frequency of haplotypes did not differ significantly between groups (χ² = 11.391, P = 0.181). Our results suggest that MIF ‐173 G/C variant increases the risk of HBV in Iranian subjects. Further studies with larger sample sizes and different ethnicities are required to validate our findings.

     

Aflatoxin-producing Aspergillus species from saffron field soils in the South Khorasan province of Iran

The aim of the present study was to isolate and identify Aspergillus species associated with saffron plants in the city of Birjand (South Khorasan Province, Iran) as well as to assess their aflatoxin B1 production. Sampling was performed during 2013–2014 crop season. Aspergillus species were isolated and purified using general and specific culture media. Growth rates and macroscopic and microscopic characteristics of the isolates were determined using yeast extract, Czapek yeast extract, malt extract and creatine sucrose agar media at 25 and 37 °C. DNA was extracted by the modified CTAB method and beta-tubulin, calmodulin and internal transcribed spacer genes were amplified and sequenced. Phylogenetic position of the isolates was determined against other Aspergillus species. Thin layer chromatography was used to investigate the production of aflatoxin B1 by Aspergillus isolates. Based on the morphological characteristics, shape and colour of the colonies, and sequencing results, the isolates belonged to Aspergillus terreus, A. flavus, A. flavipes and A. niger species. Only A. flavus isolates were aflatoxin B1 producers. We concluded that the soil of the studied saffron fields contained several species of Aspergillus, with A. flavus significantly affecting crop production through contamination of the crop by aflatoxin.