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 #
5R01DA015403-10
Application #
8590205
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
2014-01-01
Budget End
2014-12-31
Support Year
10
Fiscal Year
2014
Total Cost
$275,868
Indirect Cost
$101,268
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Lukkes, Jodi L; Freund, Nadja; Thompson, Britta S et al. (2016) Preventative treatment in an animal model of ADHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats. Eur Neuropsychopharmacol 26:1496-506
Schrantee, Anouk; Tamminga, Hyke G H; Bouziane, Cheima et al. (2016) Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial. JAMA Psychiatry 73:955-62
Freund, Nadja; Thompson, Britta S; Sonntag, Kai et al. (2016) When the party is over: depressive-like states in rats following termination of cortical D1 receptor overexpression. Psychopharmacology (Berl) 233:1191-201
Freund, Nadja; Thompson, Britta S; Norman, Kevin J et al. (2015) Developmental emergence of an obsessive-compulsive phenotype and binge behavior in rats. Psychopharmacology (Berl) 232:3173-81
Brenhouse, Heather C; Thompson, Britta S; Sonntag, Kai C et al. (2015) Extinction and reinstatement to cocaine-associated cues in male and female juvenile rats and the role of D1 dopamine receptor. Neuropharmacology 95:22-8
Andersen, Susan L (2015) Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression. Dev Psychopathol 27:477-91
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
Freund, N; Thompson, B S; Denormandie, J et al. (2013) Windows of vulnerability: maternal separation, age, and fluoxetine on adolescent depressive-like behavior in rats. Neuroscience 249:88-97

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