Early-life Experience as Determinant of Adult Emotional Behavior: Long-term effects of psychostimulant treatment.

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Early-life Experience as Determinant of Adult
Emotional Behavior Long-term effects of
psychostimulant treatment.

• Carlos A. Bolaños.
• Department of Psychology and Program in
  Neuroscience
• Florida State University, Tallahassee, FL.

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So, what we study

• How early-life experiences influences behavior
  later in life. More specifically, we study how
  exposure to drugs of abuse, (cocaine, morphine,
  amphetamine), antidepressants, and other
  psychotropic drugs, as well as physical and
  emotional stress leads to changes in brain and
  behavior during the life span.

• We use a variety of approaches behavioral,
  psychopharmacology, neurotransmitter release
  (using slice preparation), and biochemistry. We
  also use the gene transfer approach (using viral
  vectors) to regulate the expression of genes in
  discrete brain areas.

• The ultimate goal is to better understand ways in
  which developing and adult brain responds to
  environmental, pharmacological, and genetic
  insults resulting in neuropsychiatric disorders.

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Overview
Part I

• Long-term effects of methylphenidate treatment
  during postnatal development

Part II

• Preliminary findings on the long-term effects of
  physical versus emotional stress during postnatal
  development

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Attention-Deficit Hyperactivity Disorder

• ADHD is a heterogeneous neurobehavioral disorder
• Disorder can be difficult to diagnose
• It may affect up to 12 of all children
• It typically manifest by 7 years of age most
  prevalent in boys
• Three core clinical symptoms
• inattentiveness
• hyperactivity
• impulsivity

Methylphenidate (Ritalin)

• Stimulants (e.g., Ritalin) highly effective in
  treatment for ADHD
• Children as young as 2 years old are prescribed
  stimulants

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Why should we care??

• - Like other drugs with stimulant effects
  (cocaine, amphetamine, opiates, nicotine),
  methylphenidate (MPH) activates reward
  circuitry in the brain.

• - MPH exposure may result in vulnerability to
  addiction
• - Enhanced sensitivity to other drugs needing
  lower doses to get effect
• - The long-term effects of exposure to MPH (and
  many other therapeutic drugs) are not known

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the goal

• Assess the long-term behavioral reactivity to
  emotional-eliciting stimuli associated with
  early-life MPH exposure.

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Andersen, SL (2002). Neuroscience
Biobehavioral Reviews (27) 3-18.
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Strategy
PD 20
Arrival PD 14
Behavioral Testing
PD 35
weaned PD 23
Play Behavior PD 40
with mother
adulthood
MPH 2.0 mg/kg (twice daily injections)
MPH has no effect on weight gain and play
behavior in developing rats
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Juvenile MPH treatment decreases preference for
sucrose in adult rats
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Juvenile MPH treatment decreases locomotor
activity induced by a novel environment in adult
rats
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Juvenile MPH treatment increases latency to
immobility of adult rats in the FST
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MPH-treated rats show deficits in the initiation
and performance of sexual behavior during
adulthood
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Juvenile MPH results in increased anxiety in the
EPM in adult rats
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Juvenile MPH has no effect on social interaction
in adult rats
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Juvenile MPH treatment results in increased
plasma corticosterone levels in adult rats
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Summary

• Chronic exposure to methylphenidate during
  development leads to decreased sensitivity to
  rewarding stimuli and results in enhanced
  responsivity to aversive situations

• The mechanism(s) underlying these behavioral
  phenotypes remain to be elucidated

• It is conceivable that changes in neurotrophic
  factors or their signaling pathways may be
  involved.

• These results underscore the need for further
  developmental research geared toward a better
  understanding of the mechanisms underlying
  drug-induced behavioral plasticity.

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Acknowledgements
E.J. Nestler M. Barrot O. Berton D. Wallace-Black
University of Texas Southwestern Med. Ctr., Dallas