Title: Early-life Experience as Determinant of Adult Emotional Behavior: Long-term effects of psychostimulant treatment.
1Early-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.
2So, 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.
3Overview
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
4Attention-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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8Why 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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10the goal
- Assess the long-term behavioral reactivity to
emotional-eliciting stimuli associated with
early-life MPH exposure.
11Andersen, SL (2002). Neuroscience
Biobehavioral Reviews (27) 3-18.
12Strategy
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
13Juvenile MPH treatment decreases preference for
sucrose in adult rats
14Juvenile MPH treatment decreases locomotor
activity induced by a novel environment in adult
rats
15Juvenile MPH treatment increases latency to
immobility of adult rats in the FST
16MPH-treated rats show deficits in the initiation
and performance of sexual behavior during
adulthood
17Juvenile MPH results in increased anxiety in the
EPM in adult rats
18Juvenile MPH has no effect on social interaction
in adult rats
19Juvenile MPH treatment results in increased
plasma corticosterone levels in adult rats
20Summary
- 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.
21Acknowledgements
E.J. Nestler M. Barrot O. Berton D. Wallace-Black
University of Texas Southwestern Med. Ctr., Dallas