The Effects of Antidepressants on Neonatal CNS Development

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The Effects of Antidepressants on Neonatal CNS
Development
By Greg Sartor
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Introduction

• Antidepressants, particularly SSRIs, are
  prescribed to many pregnant women suffering from
  peripartum/postpartum depression, anxiety, or
  OCD, even though research has shown that these
  drugs can
• cross the placenta barrier
• penetrate the fetal BBB
• appear in breast milk. 1
• Although most doctors deem these drugs safe for
  the unborn child, there has been little research
  to determine the long-term consequences of these
  drugs on human development.

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Introduction

• In the rodent model of neonatal SSRI exposure,
  research has shown significant neurobehavioral
  and neurobiological effects
• Decreased male sexual behavior/activity 3
• Increased locomotor activity 3
• Increased ethanol consumption 2
• Increased REM sleep 4
• Decreased TPH in the Raphe Nucleus, TH in the
  Putamen, and 5-HT transporter expression in
  cortex 3

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Maciag et al
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Introduction

• The BIG hypothesis
• Animals that are exposed to SSRIs during a
  critical period of development will demonstrate
  profound and permanent neurobiological effects
  and will show conspicuous changes in their
  behavioral repertoire.

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Introduction

• Questions that I investigated
• The effects of neonatal SSRI exposure in
• Male Sexual Behavior
• Locomotor Activity
• Elevated Plus Maze
• Hypothesis
• Neonatal SSRI exposure will cause decreased male
  sexual behavior, increased locomotor activity and
  decreased time spent in open arms on EPM compared
  to the control.

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Methods

• Long Evans Rats

Critical period for 5HT and NE development
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Methods
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Methods

• Male Sexual Behavior
• Tested during dark phase of the (12/12) light
  cycle
• Acclimated 1hour in the testing room before each
  test
• Observed behaviors on video tapes (1hr)
• Mount latency
• of Mounts
• Intromission latency
• of Intromissions
• Ejaculation latency
• of Ejaculations

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Methods

• Male Sexual Behavior
• Sample video clip

Click here to play
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Methods

• Locomotor Activity
• Tested during dark phase of the (12/12) light
  cycle
• Acclimated 1hour in the testing room before each
  test
• Observed behaviors by computer program (30mins.)
• Distance Traveled (DT)
• Resting Time (RT)
• Stereotypic Time (ST)
• Ambulation Time (AT)
• Bursts of Stereotypic Movement (BSM)
• Vertical movement (V1C)

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Locomotor Activity
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Methods

• Elevated Plus Maze
• Tested during dark phase of the (12/12) light
  cycle
• Acclimated 1hour in the testing room before each
  test
• Observed behaviors on video tapes (5mins.)
• Total Crosses
• of open crosses
• of closed crosses
• Total time in open
• Total time in closed
• Total time in the middle

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Elevated Plus Maze
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Summary

• Experiment 200406
• Male sexual behavior
• No significant effects.
• Reminder In this exp. the males were injected as
  adults not as neonates.
• Experiment 200501
• Locomotor activity
• CMI females demonstrated a significant increase
  in ST activity compared to SAL females.
• Elevated Plus Maze
• CMI group showed a significant increase in the
  number of times entering the open crosses
  compared to CTM group, and CMI group showed a
  significant increase in the total times entering
  any crosses (locomotor activity) compared to SAL
  and CTM.
• Experiment 200502 03
• Locomotor activity
• No significant effects.
• Elevated Plus Maze
• MK801 demonstrated a significant decrease in the
  number of total crosses compared to CTM and CGS.
• MK801 showed a significant decrease in number of
  open crosses compared to DPAT, CTM, and CGS.
• MK801 showed a significant decrease in the time
  spent in open crosses compared to SAL, CTM, and
  CGS, and a significant increase in time spent in
  closed crosses compared to CTM and CGS.

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Conclusion

• What does all this mean?
• Questions remaining to be answered..
• Experiment 200502 200503 male sexual behavior
  and shock-induced aggression.

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Special Thanks to
Dr. Ian Paul
Lashondra Williams
Dorota Maciag
David Coppinger
Long Evans
Sharonda Swilley
Sandra OBrien
The Neuroscience Scholars Summer Program
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Questions?
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References

• 1 Cohen, L.S., Nonacs, R., Viguera, A.C., and
  Reminick, A., Diagnosis and treatment of
  depression during pregnancy. CNS Spectr,
  9(2004) 209-16.
• 2 Hilakivi, L.A., Sinclair, J.D. and Hilakivi,
  I.T., Effects on neonatal treatment with
  clomipramine on adult ethanol related behavior
  in the rat, Brain Res, 317 (1984) 129-32.
• 3 Maciag, D., Simpson, K.L., Coppinger, D., Lu,
  Y., Wang, Y, Lin, R., and Paul, I.A., Neonatal
  Antidepressant Exposure Has Lasting Effects on
  Behavior and Serotonin Circuitry,
  Neuropsychopharmacology (in press).
• 4 Mimiran, M., van de Poll, N.E., Corner, M.A.,
  van Oyen, H.G. and Bour, H.L., Suppression of
  active sleep by chronic treatment with
  chlorimipramine during early postnatal
  development effects upon adult sleep and
  behavior in the rat, Brain Res, 204 (1981)
  129-46.

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THE END