Table 6.
Overview of chemogenetic studies in animal models of depression-like behavior indicating primary findings for each specific pathway and cell-type, DREADD and the animal model employed
| Region | Model | DREADD | Route of administration | Dosing regimen | Primary findings | References |
|---|---|---|---|---|---|---|
| VTA | CUMS | rMd3(Gs) | I.P. injection | Single CNO (2 mg/kg) injection 30 min before killing | Impairing cAMP signaling via Cdk5 deletion increases susceptibility. Increasing cAMP levels rescues behavior | Zhong et al. [26] |
| NAc | CSDS | hM4(Gi) | I.P. injection | CNO (5 mg/kg) injection at 8AM and 6PM for 4.5 days following defeat | D1-MSN inhibition induces susceptibility in resilient mice | Francis et al. [32] |
| VHIP-mPFC | FST | hM3D(Gq) | I.P. injection | Single CNO (0.5 mg/kg) injection 30 min before FST | Activation mimics the anti-depressant effects of ketamine | Carreno et al. [4] |
| MDT-mPFC | TST/FST | hM3D(Gq) | I.P. injection | Single CNO (1 mg/kg) injection 30 min before FST/TST | Activation decreases immobility | Miller et al. [49] |
| LHb | CSDS | hM4D(Gi) | I.P injection | CNO (1 mg/kg) injection 12 h and 1 h before testing | Inhibition reverses CSDS induced social avoidance in 5-HT-deficient animals | Sachs et al. [52] |
| FST | hM4Di | I.P. injection | CNO (1 mg/kg) injection 30 min and 15 h following pre-test and 30 min before FST | Inhibition decreases immobility | Nair et al. [50] | |
| DRN | FST | hM3D(Gq) |
Short-term: I.P. injection Long-term: Drinking water |
Short-term: Single CNO (2 mg/kg) 45 min before behavior Long-term: CNO (5 mg/kg) in drinking water for 3 weeks |
Long-term CNO administration decreases time immobile. Short-term activation decreases time immobile and time in open arms on EPM | Urban et al. [55] |
| DRN-NAc | TST | hM3Dq | I.P. injection | Single CNO (1 mg/kg) 20 mins before testing/conditioning | Activation decreases immobility | You et al. [57] |
VTA ventral tegmental area, NAc nucleus accumbens, mPFC medial prefrontal cortex, MDT medial dorsal thalamus, LHb lateral habenula, DRN dorsal raphe nuclei, CSDS chronic social defeat stress, CUMS chronic unpredictable mild stress, FST forced swim test, TST tail suspension test, CRS chronic restraint stress