Neural Plasticity / 2012 / Article / Tab 5

Review Article

Functional Role of Adult Hippocampal Neurogenesis as a Therapeutic Strategy for Mental Disorders

Table 5

Select animal studies investigating the effect of chemical antidepressants on adult hippocampal neurogenesis and animal behavior.

SpeciesAntidepressant treatmentExperimental paradigmEffect on neurogenesisEffects on behaviorReferences

129/SvEv
Fluoxetine (SSRI):
10 mg/kg/day via drinking water for 28 days
Proliferation: BrdU (4 × 75 mg/kg, ip) at 2-hour intervals and analysis at 24 hours after last BrdU injection.
Survival: BrdU (4 × 75 mg/kg, ip) at 2-hour intervals and analysis at 28 days after last BrdU injection.
Increased cell proliferation and neuronal maturation.
Less depressive-like behavior in novelty suppressed feeding test.[47]

Sprague Dawley rat
Fluoxetine (SSRI):
5 mg/kg (ip) 1, 5, 14, 28 d.
Tranylcypromine:
7 × 7.5 mg/kg (ip) daily, then 14 × 10 mg/kg (ip) daily.
Reboxetine:
20 mg/kg, 2x per day for 21 d
Proliferation: BrdU (4 × 75 mg/kg, ip) at 2-hour intervals, then 24-hour pulsing-chase.
Survival: BrdU (4 × 75 mg/kg, ip) at 2-hour intervals, then 28-day pulsing chase.
Fluoxetine (SSRI): increased cell proliferation and neuronal maturation.
Tranylcypromine: increased cell proliferation
Reboxetine: increased cell proliferation.
NS[38]

129/SvEvFluoxetine (SSRI):
18 mg/kg daily by gavage for behavior test and via drinking water for all experiments for 5 days (subchronic) or 28 days (chronic).
Proliferation: BrdU (1 × 150 mg/kg, ip) at 2-hour pulsing chase.
Dendritic maturation, survival, and neuronal maturation: BrdU (4 × 75 mg/kg, ip over 8 hours) on day 0, started fluoxetine treatment on day 1,
and analysis on day 21 by BrdU and DCX coimmunostaining.
Increased cell proliferation in chronic treatment of fluoxetine.
No change in number of DCX+ immature neurons.
Increased dendritic length and dendritic complexity in chronic treatment of fluoxetine, but not subchronic treatment measured by BrdU+ DCX+ colabeled neurons.
Increased survival rate and neuronal maturation in chronic treatment of fluoxetine.
Less depressive-like behavior by chronic fluoxetine treatment (but not subchronic) in novelty suppressed feeding test.[48]

Nestin-CFPnuc mouseFluoxetine (SSRI): 10 mg/kg (ip) daily for 15 days.
Proliferation: BrdU (1 × 150 mg/kg, ip) and analysis 1 day later.
Survival: BrdU (1 × 150 mg/kg, ip) and analysis 30 days later.
Increased proliferation of amplifying neural progenitors (ANPs), but no change in quiescent neural progenitors (QNPs).
Increased survival rate.
NS[49]

Wistar ratEscitalopram (SSRI): 5 mg/kg (ip) for 4 weeks.BrdU (4 × 100 mg/kg, ip) with 2-hour interval during one day and analysis at 16 hours after the last BrdU injection.Increased cell proliferation in chronic treatment of escitalopram under mild stress condition, but no change under the normal condition.Chronic treatment of escitalopram shows recovery from anhedonic-like behavior caused by the mild stress condition. [50]

BALB/c mouseFluoxetine (SSRI): 10 mg/kg (ip) daily for 28 days, Imipramine (TCA): 20 mg/kg (ip) daily for 28 days.BrdU (4 × 75 mg/kg, ip) with 2 hours interval and analysis at 24 hours after last BrdU injection.
Increased cell proliferation in chronic treatment of fluoxetine and imipramine under unpredictable chronic mild stress.Chronic treatment of fluoxetine and imipramine shows recovery from depressive-like behavior caused by unpredictable chronic mild stress condition. [51]

Wistar ratLithium chloride: 2.5 mEq/kg (ip) for 14 days.BrdU (50 mg/kg, ip) daily during last 3 days of experimental periodIncreased proliferation, neuronal maturation and glial maturation of neural progenitors under normal conditions.
Lithium treatment shows recovery from neurogenesis deficits under unpredictable chronic mild stress condition.
Lithium treatment shows less depressive-like behavior under normal conditions.
Lithium treatment shows recovery from depressive-like behavior caused by unpredictable chronic mild stress condition.
[52]

*SSRI: Selective serotonin reuptake inhibitor; TCA: Tricyclic Antidepressants; DCX: doublecortin (immature neuronal marker) 13.