Table 2.
Parallels between GSK-3 inhibitors and antidepressants in adult neurogenesis and behavior.
| Phenotype | Lithium | Alternative GSK-3 inhibitors | GSK-3 deletion | Antidepressants |
|---|---|---|---|---|
| Adult neurogenesis | ↑ | ↑ (SB216763) | ↑ (Fluoxetine, tranylcypromine, reboxetine) | |
| Forced swim test (immobility) | ↓ | ↓ (CHIR99021, AR-A014418, L803mts) | ↓ (Gsk3b+/− or Gsk3a−/−) | ↓ (Fluoxetine, desipramine) |
| Exploratory behavior (hole pokes) | ↓ | ↓ (Gsk3b+/−) | ||
| Elevated zero/plus maze (time in open area) | ↑ | ↑ (Gsk3b+/−) | ↑ (Citalopram) | |
| Tail suspension test (immobility) | ↓ | ↓ (Gsk3a−/−) | ↓ (Citalopram) | |
| Novelty suppressed feeding | ↓ | ↓ (Fluoxetine, imipramine, desipramine) | ||
| Novelty induced locomotor activity | ↓ | ↓ (TDZD-8) | ↓ (Gsk3a−/−) | |
| Amphetamine induced hyperlocomotion | ↓ | ↓ (CHIR99021, TDZD-8, 6-BIO, AR-A014418, SB216763, alsterpaullone) | ↓ (Gsk3b+/−) |
Lithium stimulates adult neurogenesis and affects mammalian behaviors. Structurally diverse GSK-3 inhibitors as well as genetic loss of GSK-3 function mimic the effects of lithium, strongly implicating GSK-3 as the relevant target mediating lithium effects on behavior. Interestingly, distinct classes of antidepressants have similar effects as lithium on neurogenesis and many behaviors.