Topic: Deschloroclozapine

The brainstem locus coeruleus (LC) is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline (NA) is a neuromodulator involved in the regulation of excitability of brain networks. In this study, we investigated whether chemogenetic activation of the LC is able to induce hippocampal noradrenaline release and affects hippocampal excitability.Male Sprague Dawley rats (n=8) were injected with the viral vector CAV2-PRSx8-hM3Dq in the LC for expression of hM3Dq, which allows chemogenetic LC activation upon systemic injection with deschloroclozapine (DCZ). Rats w

Designer receptors exclusively activated by designer drugs (DREADD) are chemogenetic tools that enable the selective activation or silencing of neurons in a given brain area. According to classical findings on the role of the lateral hypothalamic area (LHA) in hunger, we hypothesized that selective silencing of the LHA may decrease food intake.We bilaterally injected adeno-associated viral (AAV) vectors carrying the gene of a modified M4 muscarinic acetylcholine receptor into the LHA of rats. Later, rats were treated with DREADD actuator agents and food intake was measured in a 30 min time-win

Microglia seem able to alter the excitatory/inhibitory balance in temporal lobe epilepsy (TLE). Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable cell-specific modulation. We aim to investigate whether Gi-DREADD-based modulation of microglia reduces the amount of spontaneous recurrent seizures (SRS) in a mouse model of TLE.CX3CR1CreERT2/CreERT2 mice were crossed with R26LSL-Gi-DREADD/LSL-Gi-DREADD mice to obtain CX3CR1CreERT2/+:R26LSL-Gi-DREADD/+ and CX3CR1CreERT2/+:R26+/+ mice, as controls. Tamoxifen was administered to induce Gi-DREADD expression in CX3CR1+ cells. F

A critical advance in neuroscience is the ability to intervene reversibly in a pathway-specific manner on interactions between brain regions, providing understanding of the causal role of those interactions, but also moving us towards targeted therapies for pathologies linked to neural pathways. We present data on pathway-specific DREADDs (Designer Receptor Exclusively Activated by Designer Drugs) in macaque monkeys. This approach is only now emerging for primates, and permits the targeted modulation of a specific neural pathway over a period of hours. We conducted two DREADD experiments to sp