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

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. So, what we study….

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

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  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 1897: Restless, teething Infants? Toothache? Cough? Try Bayer… Heroin, Cocaine

  6. 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

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

  8. Andersen, SL (2002). Neuroscience & Biobehavioral Reviews (27) 3-18.

  9. Strategy Arrival: PD 14 PD 20 weaned: PD 23 PD 35 Play Behavior: PD 40 Behavioral Testing with mother adulthood MPH 2.0 mg/kg (twice daily injections) MPH has no effect on weight gain and play behavior in developing rats

  10. Juvenile MPH treatment decreases preference for sucrose in adult rats

  11. Juvenile MPH treatment decreases locomotor activity induced by a novel environment in adult rats

  12. Juvenile MPH treatment increases latency to immobility of adult rats in the FST

  13. MPH-treated rats show deficits in the initiation and performance of sexual behavior during adulthood

  14. Juvenile MPH results in increased anxiety in the EPM in adult rats

  15. Juvenile MPH has no effect on social interaction in adult rats

  16. Juvenile MPH treatment results in increased plasma corticosterone levels in adult rats

  17. 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.

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

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