clozapine-n-oxide and 1-(3-chlorophenyl)piperazine

The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of G

Topics: Animals; Anti-Anxiety Agents; Anxiety; Brain Mapping; Cannabinoid Receptor Antagonists; Clozapine; Dark Adaptation; Disease Models, Animal; Estrenes; Excitatory Postsynaptic Potentials; Exploratory Behavior; Green Fluorescent Proteins; GTP-Binding Protein alpha Subunits, Gq-G11; In Vitro Techniques; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Phosphodiesterase Inhibitors; Piperazines; Pyrrolidinones; Receptors, Drug; Rimonabant; RNA, Messenger; Septal Nuclei; Serotonin Receptor Agonists; Signal Transduction; Sodium Channel Blockers; Tetrodotoxin; Vesicular Inhibitory Amino Acid Transport Proteins