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

More on renormalizable exceptions to Nelson-Seiberg theorem

The Nelson-Seiberg theorem dictates conditions for the spontaneous breaking of the supersymmetry in Wess-Zumino models with generic, possibly non-renormalizable, superpotential; the existence of the R-symmetry is necessary while the spontaneous breaking of the R-symmetry is sufficient. If we restrict ourselves to generic but renormalizable theories, however, there exist Wess-Zumino models whose vacua break the R-symmetry spontaneously while preserving the supersymmetry. The classification and conditions of such renormalizable exceptions are under active study. We give some new examples of spontaneous breaking of the R-symmetry with preserved supersymmetry that are not covered in the literature.Comment: 10 pages, v2: reference update

New Constraints on Radiative Decay of Long-Lived Particles in Big Bang Nucleosynthesis with New 4^4He Photodisintegration Data

A recent measurement of $^4$He photodisintegration reactions, $^4$He($\gamma$,$p$)$^3$H and $^4$He($\gamma$,$n$)$^3$He with laser-Compton photons shows smaller cross sections than those estimated by other previous experiments at $E_\gamma \lesssim 30$ MeV. We study big-bang nucleosynthesis with the radiative particle decay using the new photodisintegration cross sections of $^4$He as well as previous data. The sensitivity of the yields of all light elements D, T, $^3$He, $^4$He, $^6$Li, $^7$Li and $^7$Be to the cross sections is investigated. The change of the cross sections has an influence on the non-thermal yields of D, $^3$He and $^4$He. On the other hand, the non-thermal $^6$Li production is not sensitive to the change of the cross sections at this low energy, since the non-thermal secondary synthesis of $^6$Li needs energetic photons of $E_\gamma \gtrsim 50$ MeV. The non-thermal nucleosynthesis triggered by the radiative particle decay is one of candidates of the production mechanism of $^6$Li observed in metal-poor halo stars (MPHSs). In the parameter region of the radiative particle lifetime and the emitted photon energy which satisfies the $^6$Li production above the abundance level observed in MPHSs, the change of the photodisintegration cross sections at $E_\gamma \lesssim 30$ MeV as measured in the recent experiment leads to $\sim 10$% reduction of resulting $^3$He abundance, whereas the $^6$Li abundance does not change for this change of the cross sections of $^4$He($\gamma$,$p$)$^3$H and $^4$He($\gamma$,$n$)$^3$He. The $^6$Li abundance, however, could show a sizable change and therefore the future precise measurement of the cross sections at high energy $E_\gamma \gtrsim$ 50 MeV is highly required.Comment: 10 pages, 7 figures, conclusion not changed, to be published in PR