+
Mentor:
Matthew Roesch
Team Members:
Brian Barnett
Valerie Cohen
Taylor Hearn
Emily Jones
Reshma Kariyil
Alice Kunin
Sen Kwak
Jessica Lee
Brooke Lubinski
Gautam Rao
Ashley Zhan

+
 ADHD (Attention Deficit Hyperactivity Disorder)

“In 30 years there has been a twentyfold increase in the consumption of drugs for attentiondeficit 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

+
 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

+
 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)

+
 Dorsal Prelimbic Cortex (dPL)
 Previously associated with controlling impulsive behavior
 Pharmacology
 Dopamine & DAT
 Noradrenaline
 Monoamine oxidase
 Nicotine
(Vertes, 2004)

+
 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

+
 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)

+
 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.

+
(Schoenbaum, 2000)
Variables
 Independent Variables
 Drug administration
 Stop-signal timing
 Dependent Variables
 Neural recording
 Task performance
 Rat behavior
Test Groups
 Control: Control rats + saline
 Experimental 1: Fetal Nicotine rats + saline
 Experimental 2: Fetal Nicotine rats + Adderall
(Bari et al., 2011)

+

+
Spring
2012
IACUC approval
Apply for grants
Build electrodes
Summer
2012
Fetal
Nicotine
Pilot Study
Fall 2012
Exp.
Group 1
Control
Group
Junior
Colloquia
Spring
2013
Exp.
Group 1
Exp.
Group 2
Histology
Studies
Fall 2013
Data analysis
Write
Thesis paper
Spring
2014
Complete
Thesis paper
Senior
Thesis
Conference

+
 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

+

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.

+