Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, residente-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants

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多胡圭一教授國井和郎教授退官記念

Analytical study of the dynamical behavior of loading buckets interacting with bulk materials

A new analytical model has been developed to calculate the dynamical behavior of a column on which buckets loading and interacting with bulk materials, such as iron ore and coal with various grain sizes, are set. A set of linear equations of motion was obtained by considering the effective load, the stiffness, and the friction of materials. From the analysis of the equation, the growth of vibration in a column was indicated, which was caused by the cross term of a stiffness matrix because of the interaction between buckets and a material. In addition, bucket speed was found to affect the damping of the vibration through the critical condition ∆xω~v B where ∆x is bucket displacement, ω is the characteristic frequency of a column , and v is bucket speed. A simplified characteristic function was obtained for the stability of a system and compared with the results of a laboratory-scale experiment in order to evaluate the analytical model

Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide (CGRP)-containing nerves in rat mesenteric arteries

The present study was designed to investigate involvement of angiotensin (Ang) II type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 μg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI)- and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the Sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.</p