Transcript Thesis Proposal Presentation

+ TEAM RITALIN
Mentor:
Matthew Roesch
Team Members:
Research in Testing ADHD's
Link to Impulsivity in
Neuroscience
Brian Barnett
Valerie Cohen
Taylor Hearn
Emily Jones
Reshma Kariyil
Alice Kunin
Sen Kwak
Jessica Lee
Brooke Lubinski
Gautam Rao
Ashley Zhan
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Introduction
 ADHD
(Attention Deficit Hyperactivity Disorder)
“In 30 years there has been a twentyfold increase in the
consumption of drugs for attention-deficit disorder”

(Sroufe, 2012)

Limited research on the neurobiology of the disorder
Diagnoses are made based on subjective, behavioral
observations rather than reliable objective identifiers

Frequent
misdiagnoses and rising medical costs
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Importance of Our Project

No valid animal model of ADHD developed yet

Women who smoke during pregnancy are three times as
likely to have children diagnosed with ADHD
(Linnet et al., 2005)

Validating the fetal nicotine rat model to further study
ADHD

Research valuable to scientists, psychiatrists,
pharmacists, drug companies, patients, and relatives of
patients
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Literature Review: Impulsivity


Impulsivity

Clinical characteristic of ADHD

The ability to stop an ongoing or habitual movement
Stop-Signal Task

Performance is worse in humans with ADHD and in proposed
animal models of ADHD
(Bari et al., 2011)
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Literature Review: Neurophysiology

Dorsal Prelimbic Cortex (dPL)


Previously associated with controlling impulsive behavior
Pharmacology

Dopamine & DAT

Noradrenaline

Monoamine oxidase

Nicotine
(Vertes, 2004)
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Literature Review: Adderall

25% of all prescriptions written for ADHD
(Sallee & Smirnoff, 2004)

Composed of D-amphetamine and L-amphetamine

Increases the amount of postsynaptic dopamine and
noradrenaline

Change in conformation and inhibition of dopamine
transporter

Inhibition of monoamine oxidases A and B
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Literature Review: Fetal Nicotine Rats

Face validity: increased stop-signal reaction time,
decreased percent correct stop trials

Construct validity: decreased firing in the dPL cortex
following stop signal

Predictive validity: altered dPL firing and stop-signal
performance reversed by Adderall administration
(Sontag, Tucha, Wlitza, & Lange, 2009)
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Research Questions & Hypotheses

How will neural firing in the dorsal prelimbic cortex and stopsignal task performance differ between control, fetal nicotine,
and Adderall-administered rats? Will these neural differences
be sufficient to validate the fetal nicotine rat as an animal
model of ADHD?

Hypothesis: Fetal nicotine rats will exhibit reduced neural firing
in the dPL cortex and worsened stop-signal task performance
as compared to the control group. Adderall administration will
increase dPL activity and improve task performance in fetal
nicotine rats.
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Methodology: Variables
Variables


(Schoenbaum, 2000)
Test Groups

Control: Control rats + saline

Experimental 1: Fetal Nicotine
rats + saline

Experimental 2: Fetal Nicotine
rats + Adderall
Independent Variables

Drug administration

Stop-signal timing
Dependent Variables

Neural recording

Task performance

Rat behavior
(Bari et al., 2011)
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Methodology: Procedure
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Timeline
Spring
2012
Summer
2012
Fall 2012
Spring
2013
Fall 2013
Spring
2014
Exp.
Group 1
Exp.
Group 1
Data
analysis
Complete
Thesis
paper
Apply for
grants
Control
Group
Exp.
Group 2
Write
Thesis
paper
Senior
Thesis
Conference
Build
electrodes
Junior
Colloquia
Histology
Studies
IACUC
approval
Fetal
Nicotine
Pilot Study
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Anticipated Results & Scientific
Impact

Physiological & neurotransmitter pathway disruption in inhibiting
impulsivity

Repaired with Adderall

Nicotine exposure as cause of ADHD

Fetal nicotine rats as valid model of ADHD

Applicable to humans
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References

Bari, A., Mar, A.C., Theobald, D.E., Elands, S.A., Oganya, K.C., Eagle, D.M. & Robbins, T.W. (2011) Prefrontal
and monoaminergic contributions to stop-signal task performance in rats. Journal of Neuroscience, 31,
9254-9263.

Jensen, P.S., Kettle, L., Roper, M.T., Sloan, M.T., Dulcan, M.K., Hoven, C., Bird, H.R., Bauermiester, J.J., &
Payne, J.D. (1999). Are stimulants overprescribed? treatment of ADHD in four U.S. communities. Journal of
the American Academy of Child & Adolescent Psychiatry, 38, 794-804.

Linnet, K., Wisborg, K., Obel, C., Secher, N.J., Thomsen, P.H., Agerbo, E., & Henriksen, T.B. (2005) Smoking
during pregnancy and the risk for hyperkinetic disorder in offspring. Pediatrics, 116(2), 462-467.

Sallee, F. R., & Smirnoff, A. V. (2004). Adderall XR: long acting stimulant for single daily dosing. Expert
Review of Neurotherapeutics, 4(6), 927-934. doi: 10.1586/14737175.4.6.927

Schoenbaum, G. Olfactory Learning and the Neurophysiological Study of Rat Prefrontal Function. In:
CRC Series: Methods and Frontiers in Neuroscience. Edited by S.A. Simon and M.A.L. Nicolelis, CRC
Press, NY, 2000.

Sontag, T. A., Tucha, O., Walitza, S., & Lange, K. W. (2010). Animal models of attention deficit/hyperactivity
disorder (ADHD): a critical review. ADHD Attention Deficit and Hyperactivity Disorders, 2(1), 1-20. doi:
10.1007/s12402-010-0019-x

Sroufe, A. L. (2012, January 28). Ritalin Gone Wrong. The New York Times. Retrieved from
http://www.nytimes.com/2012/01/29/opinion/sunday/childrens-add-drugs-dont-work-longterm.html?_r=1&pagewanted=all

Vertes, R. P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse. 51
32-58. DOI 10.1002/syn.10279.
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Questions?