Neural Plasticity / 2012 / Article / Tab 3

Review Article

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

Table 3

Select animal studies investigating the effect of drug addiction on adult hippocampal neurogenesis.

SpeciesDrug treatmentExperimental approachEffect on neurogenesisReferences

Cocaine

Cocaine/rat (Sprague-Dawley)Self-administration (0.5 mg/kg infusion, iv) for 3 weeks.Proliferation: BrdU (150 mg/kg, ip) once at 2-hours pulsing chase after the last self-administration session.
Survival: BrdU at four-week pulsing chase after last self-administration session.
Cell proliferation: decreased number of BrdU+ cells.
Survival: no change.
[27]

Cocaine/rat (Sprague-Dawley)20 mg/kg (ip) for either 1 or 14 daysBrdU once (100 mg/kg, ip) at 2-hour pulsing chase on either 1 or 14 days during cocaine exposure.One-day cocaine injection: no change in cell proliferation
Fourteen-day cocaine injection: decreased cell proliferation
[28, 29]

Sprague-Dawley ratSelf-administration (0.5 mg/kg/20 s or 1.5 mg/kg/20 s infusion, iv) for 2 weeks.Proliferation: BrdU (3 × 50 mg/kg, ip) at 4-hour intervals; analysis twenty-four hours after last BrdU injection.
Survival: BrdU (3 × 50 mg/kg, ip) at 4-hour intervals; analysis 4 weeks after last BrdU injection.
Proliferation: decreased number of BrdU+ cells.
Survival: decreased neurogenesis.
[30]

Cocaine/rat (Wistar)20 mg/kg (ip) once daily for 8 days.BrdU once (40 mg/kg, ip) at 2-hour pulsing chase on final day of cocaine exposure.Decreased number of BrdU+ cells for cell proliferation.
Decreased number of Ki67+ cells with no statistical significance.
[31]

Cocaine/rat (Wistar)20 mg/kg (ip) daily for 24 days.BrdU (40 mg/kg, ip) daily for 7 days during the first 7days of cocaine exposure and Ki67 immunostaining.Decreased number of Ki67+ cells for cell proliferation.
No effect on survival.
[31]

Cocaine/rat (Wistar)20 mg/kg (ip) daily for either 8 or 24 days.BrdU (2 × 140mg/kg, ip) at 6-hour intervals and 24hours before receiving cocaine exposure.Both 8-and 24-day cocaine injection: no effect on maturation [31]

Alcohol

Sprague-Dawley ratAcute: EtOH (5 g/kg) by gavage.
Chronic: EtOH (5 g/kg) via intragastric catheter on every 8 hours for 4 days.
Proliferation:
Acute: BrdU (2 × 100 mg/kg, ip) at 4 hours 15 minutes and 2 hours and 15 minutes pulsing chase.
Chronic: BrdU (4 × 100 mg/kg, ip) daily for 4-day binge EtOH
Survival:
Acute: BrdU (2 × 100 mg/kg, ip) at 4-week pulsing chase.
Chronic: BrdU (4 × 50 mg/kg, ip) at 4-week pulsing chase.
Acute: both proliferation and neuronal maturation decreased.
Chronic: both proliferation and neuronal maturation decreased.
[32]

Sprague-Dawley ratEtOH (final concentration, 6.4% vol/vol) by gavage for 6 weeks.Proliferation: BrdU (7 × 40 mg/kg, ip) at 2-hour intervals; animals were sacrificed 1 hour after last BrdU injection.
Survival: BrdU (40 mg/kg, ip) once daily for first 10 days of 6 weeks EtOH binge; animals were sacrificed 32 days after the last dose of EtOH.
Proliferation: decreased cell proliferation.
Maturation and survival: decreased neuronal maturation.
[33]

Wistar ratAlcohol nondependent: Self-administered alcohol for 3 weeks and exposed air for 10 weeks.
Alcohol dependent:
Self-administered alcohol for 3 weeks and exposed to intermittent alcohol vapors for 10 weeks.
At week 6, BrdU (150 mg/kg, ip) at 4-week pulsing chase.
Immunostaining:
Fluoro-Jade C: cell death neuronal degeneration
AC-3: apoptotic cells.
Ki-67: proliferating cells.
DCX: immature neurons.
NeuN: mature neurons.
Nondependent drinking:
increased cell death and decreased cell proliferation, immature neurons and survival.
Dependent drinking:
increased cell death and decreased cell proliferation, immature neurons and survival.
[34]

C57BL/6J mouseEtOH by gavage for 28 days and abstinence for either 1 or 14 days.BrdU (3 × 300 mg/kg, ip) at 4 weeks pulsing chase.
Immunostaining: 
DCX: immature neurons
PCNA: proliferating cell marker
Behavior tests:
open-field locomotor activity and forced swimming test.
Abstinence following alcohol drinking caused:
(i) no change in survival of neuronal progenitor cells.
(ii) decreased proliferative activity of progenitor cells.
(iii) decreased neurogenesis.
(iv) increased depressive-like behavior.
(v) transiently (1 day abstinence) increased locomotor activity.
[35]

Rhesus MonkeyAlcohol induction: EtOH (1%) by gavage for 40 sessions.
Alcohol self-administration: EtOH (6%) by gavage for 200 sessions over 11 months.
Alcohol abstinence:
abstinence for 2–2.5 months.
Immunostaining:
Fluoro-Jade C: cell death neuronal degeneration
AC-3: apoptotic cells.
Ki-67: proliferating cells.
GFAP: radial glia-like stem cell and astrocyte marker.
SOX2: amplifying neural progenitor cell marker.
NeuroD1: immature neurons.
PSA-NCAM: mature neurons.
Abstinence following alcohol drinking caused:
(i) decreased neurogenesis,
(ii) decreased proliferative activity of progenitor cells in initial phases of neuronal development.
[36]