TABLE 2.
Effects of modulating HCN2 expression and function on depression-like behavior.
| HCN channels | |||
|---|---|---|---|
| Intervention | Affected brain region | Results | References |
| CUMS | VTA | Decreased DA neuronal firing and I(h) | Zhong et al. (2018) |
| Increased depression-like behavior | |||
| CSDS | VTA | Increased DA neuronal firing and I(h) | Cao et al. (2010) |
| Increased depression-like behavior | Chaudhury et al. (2013) | ||
| CSDS | NAc | Decreased HCN 2 expression and I(h) in ChIN | Cheng et al. (2019) |
| P11 −/− | Increased depression-like behavior | ||
| HCN1 −/− | Global knockout | Decreased time spent immobile in TST and FST; increased social interaction | Lewis et al. (2011) |
| HCN2 −/− | |||
| TRIP8b −/− | |||
| HCN2 antagonist | |||
| ZD7288 (on NAc slices) | NAc | Decrease ChIN firing | Cheng et al. (2019) |
| ZD7288 (into VTA) | VTA | Reverse CSDS-induced social avoidance | Cao et al. (2010) |
| DK-AH 269 (into VTA) | |||
| I(h) potentiator | |||
| Lamotrigine (into VTA, for 5 days) | VTA | Reversed CSDS-induced social avoidance and decrease in sucrose preference | Friedman et al. (2014) |
| HCN2 overexpression | NAc ChIN | Reversed social avoidance in CSDS susceptible mice as well as depressogenic behavior in SPT, TST and FST in p11−/− mice | Cheng et al. (2019) |
| HSV-LS1L-HCN2-eYFP/AAV2-FLEX-HCN2 | |||
| AAV2-HCN2-eGFP/HSV-LS1L-HCN2 | VTA DA | Reverse CSDS- and CUMS-induced depression- and anxiety-like behaviors in SPT, FST, NSFT and social interaction test | Zhong et al. (2018) |
| Friedman et al. (2014) | |||
| HCN2 knockdown | |||
| AAV2-HCN2shRNA-eGFP | VTA DA | Decreased sucrose preference in SPT, increased immobility time in FST, increased latency to feed in NSFT and decreased time spent in open arms of EPM | Zhong et al. (2018) |
| HCN1 knockdown | |||
| LV-HCN1-shRNA | Dorsal hippocampus | Increased the time spent in the centre of OFT and in the open arms of EPM, decreased time spent immobile in FST | Kim et al. (2012) |
ChIN, cholinergic interneurons; CUMS, chronic unpredictable mild stress; DA, dopamine; I(h), cationic current through HCN channels; FST, forced swim test; NAc, nucleus accumbens; NSFT, novelty suppressed feeding test; OFT, open field test; SPT, sucrose preference test; VTA, ventral tegmental area.