Consistent with PA-08-217, "Drug Abuse Prevention Intervention Research", we propose to study neurobiological mechanisms that underlie currently recognized commonalities in behavioral manifestations of attention deficit hyperactivity disorder (ADHD) and drug addiction. Alterations in cortical dopamine systems may play a prominent role in ADHD, and that the beneficial effects of stimulant therapies (e.g. methylphenidate (MPH), amphetamines) lies in their ability to reduce abnormalities in prefrontal dopamine function. In this competitive renewal, we would like to continue our work on the relationship between stimulant therapy in juvenile rats and later drug-seeking behavior. Here, we will build upon our findings to: 1) directly confirm our preliminary observations regarding untoward later consequences of abnormalities in juvenile cortical dopamine function;2) continue to explore gender-related differences in the effects of early stimulant treatment;and 3) further define dopaminergic consequences of stimulant exposure during the juvenile period that may underlie later behavioral attributes of addiction. We will use behavioral, neurochemical, and neuroanatomical approaches to investigate prefrontal dopamine function and the emergence of substance abuse-related problems. Most importantly, we will use this information to develop new, preventative strategies that may be used to reduce drug abuse in this high-risk population.

Public Health Relevance

We propose to study neurobiological mechanisms that underlie currently recognized commonalities in behavioral manifestations of attention deficit hyperactivity disorder (ADHD) and drug addiction. We will use behavioral, neurochemical, and neuroanatomical approaches to investigate prefrontal dopamine function and the emergence of substance abuse-related problems with the goal of developing new, preventative strategies that may be used to reduce drug abuse in this high-risk population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015403-08
Application #
8211086
Study Section
Special Emphasis Panel (ZRG1-PMDA-A (01))
Program Officer
Frankenheim, Jerry
Project Start
2002-07-01
Project End
2014-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
8
Fiscal Year
2012
Total Cost
$306,520
Indirect Cost
$112,520
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Stanis, Jessica J; Andersen, Susan L (2014) Reducing substance use during adolescence: a translational framework for prevention. Psychopharmacology (Berl) 231:1437-53
Sonntag, Kai C; Brenhouse, Heather C; Freund, Nadja et al. (2014) Viral over-expression of D1 dopamine receptors in the prefrontal cortex increase high-risk behaviors in adults: comparison with adolescents. Psychopharmacology (Berl) 231:1615-26
Freund, Nadja; MacGillivilray, Heather T; Thompson, Britta S et al. (2014) Sex-dependent changes in ADHD-like behaviors in juvenile rats following cortical dopamine depletion. Behav Brain Res 270:357-63
Stephan, Alexander H; Madison, Daniel V; Mateos, Jose Maria et al. (2013) A dramatic increase of C1q protein in the CNS during normal aging. J Neurosci 33:13460-74
Andersen, Susan L; Navalta, Carryl P (2011) Annual Research Review: New frontiers in developmental neuropharmacology: can long-term therapeutic effects of drugs be optimized through carefully timed early intervention? J Child Psychol Psychiatry 52:476-503
Andersen, Susan L; Teicher, Martin H (2009) Desperately driven and no brakes: developmental stress exposure and subsequent risk for substance abuse. Neurosci Biobehav Rev 33:516-24
Brenhouse, Heather C; Napierata, Lee; Kussmaul, Lucinda et al. (2009) Juvenile methylphenidate exposure and factors that influence incentive processing. Dev Neurosci 31:95-106
Andersen, Susan L; Napierata, Lee; Brenhouse, Heather C et al. (2008) Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors. Eur J Neurosci 27:2962-72
Brenhouse, Heather C; Sonntag, Kai C; Andersen, Susan L (2008) Transient D1 dopamine receptor expression on prefrontal cortex projection neurons: relationship to enhanced motivational salience of drug cues in adolescence. J Neurosci 28:2375-82
Mague, Stephen D; Andersen, Susan L; Carlezon Jr, William A (2005) Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats. Biol Psychiatry 57:120-5

Showing the most recent 10 out of 11 publications