Combination of fluoxetine and extinction treatments forms a unique synaptic protein profile that correlates with long-term fear reduction in adult mice

Peer reviewe

Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation. Significant correlations between the AUC/D of tacrolimus and everolimus were found for patients with the CYP3A5*1 allele or CYP3A5*3/*3 at both one month and one year. At both stages, the determination coefficients were higher and the slopes of regression equations were larger for patients with CYP3A5*3/*3 compared to the CYP3A5*1 allele. A good correlation between single doses of tacrolimus and everolimus was found for CYP3A5*3/*3 patients at 1 year after transplantation (r = 0.794, p < 0.001). The variability of the AUC0–24/D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC0–12/D of everolimus. Clinicians may be able to comprehensively carry out the dose adjustments of tacrolimus and everolimus based on relationship with AUCs of both drugs in each CYP3A5 genotype

The Effect of Serotonin Receptor 5-HT1B on Lateral Inhibition between Spiny Projection Neurons in the Mouse Striatum

The principal neurons of the striatum, the spiny projection neurons (SPNs), make inhibitory synaptic connections with each other via collaterals of their main axon, forming a local lateral inhibition network. Serotonin, acting via the 5-HT1B receptor, modulates neurotransmitter release from SPN terminals in striatal output nuclei, but the role of 5-HT1B receptors in lateral inhibition among SPNs in the striatum is unknown. Here, we report the effects of 5-HT1B receptor activation on lateral inhibition in the mouse striatum. Whole-cell recordings were made from SPNs in acute brain slices of either sex, while optogenetically activating presynaptic SPNs or fast-spiking interneurons (FSIs). Activation of 5-HT1B receptors significantly reduced the amplitude of IPSCs evoked by optical stimulation of both direct and indirect pathway SPNs. This reduction was blocked by application of a 5-HT1B receptor antagonist. Activation of 5-HT1B receptors did not reduce the amplitude of IPSCs evoked from FSIs. These results suggest a new role for serotonin as a modulator of lateral inhibition among striatal SPNs. The 5-HT1B receptor may, therefore, be a suitable target for future behavioral experiments investigating the currently unknown role of lateral inhibition in the function of the striatum