Susan L Andersen
Mc Lean Hospital (belmont, Ma)
Project start date: 2002-07-01
Project end date: 2014-12-31
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Early Drug Exposure And Drug Reward Mechanisms
Susan L Andersen, Associate Professor
Mc Lean Hospital (belmont, Ma)
115 Mill St
belmont, Ma 02478
Grant 5R01DA015403-05 from National Institute On Drug Abuse IRG: IFCN
Abstract: Attention-deficit/hyperactivity disorder (ADHD) affects attention and motor capacities in approximately 6% of school-aged children, making it the most prevalent childhood disorder. ADHD can be treated effectively with stimulants including methylphenidate (MPH; RitalinTM), which are indirect dopamine (DA) agonists, and their use is rising. However, the use of such stimulants has been limited by concerns over their abuse or the possible role they play as a "gateway" to the abuse of other substances. Recent clinical data show that ADHD children treated with stimulants experience an 85% reduction in substance abuse compared with those who do not receive pharmacotherapy. The interpretation of these clinical observations, however, is difficult since effectively treated ADHD patients have improved psychosocial and academic skills that reduce other risk factors, such as social impairment. In addition, they do not address potential mechanisms leading to alternative interpretations including the possibility that early treatment with MPH can imprint on the underlying neurobiological substrate of stimulant abuse. In other words, juvenile exposure to MPH potentially can produce enduring effects on the neurobiology of the developing brain that outlast the period of drug treatment itself. Some of these questions can potentially be answered using animal models and it has been shown that chronic exposure to stimulant drugs, such as MPH, causes long-lasting increases in rewarding effects, thereby increasing vulnerability to substance abuse. However, these studies have been performed in adult animals limiting their interpretation for drug treatment in juvenile (developing) brains. We have, therefore, developed an animal model using MPH exposure in juvenile rats. In this model, MPH exposure made moderate doses of cocaine aversive and high doses less rewarding later in life demonstrating reduced vulnerability to stimulant abuse. Thus, our results indicate that imprinting and/or age differences in pharmacokinetics of MPH could mediate its enduring effects. In the proposed set of studies we endeavor to determine 1) the age-related contribution of bioavailability of MPH to cocaine reward later in life; 2) the effect of chronic MPH treatment on dopamine release in the pre-pubertal rat; 3) whether pre-pubertal exposure to MPH changes dopamine receptor expression; and 4) the role of dopamine in the underlying mechanism of MPH-induced changes in the pre-pubertal rat
Keywords: attention deficit disorder, behavioral medicine, developmental neurobiology, dopamine agonist, drug abuse prevention, drug addiction antagonist, early experience, juvenile animal, methylphenidate, nonhuman therapy evaluation, pediatric pharmacology, pharmacokinetics age difference, cocaine, dopamine receptor, drug administration rate /duration, receptor expression behavioral /social science research tag, laboratory rat, outcomes research
Project start date: 2003-09-30
Project end date: 2008-06-30
5R01DA015403-05 (2007): $187266
5R01DA015403-04 (2006): $191834
5R01DA015403-03 (2005): $196834
5R01DA015403-02 (2004): $221958
Grants awarded to Susan L Andersen
REPRESENTATIONS OF SIGNIFICANT OTHERS IN SOCIAL JUDGMENT
Susan L Andersen, Associate Professor
New York University Office Of Sponsored Programs New York, Ny 100122331
Grant 5R01MH048789-04 from National Institute Of Mental Health IRG: BSR
Abstract: Until recently, little was known about whether or not social constructs representing a specific person could be utilized in general social perception, even though theories of personality and behavior have long proposed that knowledge of significant other influences how people conceptualize and respond emotionally to various other individuals. Recent research, however, has shown that people may often more or less assimilate a new person they meet to a significant-other representation stored in memory, such that new the person is (a) remembered as having qualities he/she does not have because they describe the representation and (b) is affectively evaluated accordingly. These data constitute the first experimental demonstration of the classic concept of "transference," leaving aside assumptions about parental, early-childhood, and biological influences, and the focus on patients and therapists. The data demonstrate transferential processing in everyday social judgment and are important because this notion is the basis of the widely held clinical assumption that much human suffering results from inappropriately superimposing old interpersonal patterns learned with significant others onto other individuals in one s life. If there is any truth to this assumption, the mental health implications of well-controlled experimental investigations of transferential processing could be vast. The general aim of the proposed research is to illucidate the phenomenon of transferential processing while contributing to basic research in social cognition about category structure, activation, and function in this highly personal and interpersonal domain. The fifteen studies proposed constitute a programmatic body of work designed to examine cognitive processes underlying activation of significant-other representations, cognitive properties of these representations, and consequences for schema-triggered affect and behavior. Because this work has important implications for cognition, affect, and behavior, it necessarily involves multiple paradigms. All the proposed methods, however, derive from experimental social psychology and social information processing. They are also entirely idiographic, which in itself constitutes a contribution to basic research. The proposed studies will employ state-of-the-art procedures to illucidate a problem of longstanding clinical interest and will thus have clear mental health implications while being firmly grounded in the domain of social cognition.
Keywords: dyadic interaction, interpersonal relations, judgment, social behavior, behavior, cognition, cue, early experience, emotion, memory, self concept, stimulus /response, suggestion, visual stimulus, computer program /software, human subject, microcomputer, psychological test
Project start date: 1992-03-01
Project end date: 1997-02-28
5R01MH048789-04 (1995): $114046
5R01MH048789-03 (1994): $113297
5R01MH048789-02 (1993): $106913
1R01MH048789-01 (1992): $101040
Translational Imaging Of Methylphenidate Exposure
Susan L Andersen, Associate Professor
Mc Lean Hospital (belmont, Ma) 115 Mill St Belmont, Ma 02478
Grant 1R03DA016696-01 from National Institute On Drug Abuse IRG: ZDA1
Abstract: In this I/START application from a junior investigator, we propose to use magnetic resonance imaging (MRI) in animals to test the hypothesis that early exposure to methylphenidate (MPH) alters neurobiological development. Stimulants, such as MPH, are the treatment of choice for children with Attention Deficit/Hyperactivity Disorder (ADHD), which is one of the most prevalent childhood disorders and affects an average of 6% of the population. Even though stimulants have been used to treat ADHD since the 1950 s, we know very little about the long-term enduring effects of pharmacotherapy on the developing brain. Research on this topic has become even more imperative, as children are being treated more aggressively and earlier (as young as 2 years of age) with pharmacotherapy for ADHD. From the adult preclinical literature, we know that exposure to stimulants produces enduring changes in the underlying neurobiology and neuroanatomy of the reward systems. In our animal model of childhood exposure to stimulants, we have shown that pre-pubertal exposure to the stimulant MPH produces different - even opposite - enduring changes than post-pubertal exposure (Andersen et al., 2002). This increase in the aversive properties of cocaine following pre-pubertal MPH exposure parallels clinical observations of reduced substance use disorder in adolescents who had received pharmacotherapy for their ADHD (Biederman et al., 1999). Funding from the I/START initiative will enable the PI to expand her basic research interests as a developmental psychopharmacologist to the more clinically relevant domain of neuroimaging. Preliminary MRI data will be collected and analyzed in animals that have been exposed to MPH pre-pubertally for the "proof of concept" that early medication produces enduring and specific changes in brain activity. These important pilot data will then serve as the basis for an R01 application that will determine the nature and mechanism by which early drug exposure imprints on brain activity in rats and humans.
Keywords: attention deficit disorder, brain imaging /visualization /scanning, methylphenidate, developmental neurobiology, drug adverse effect, autoradiography, bioimaging /biomedical imaging, laboratory rat, magnetic resonance imaging
Project start date: 2003-05-01
Project end date: 2005-04-30
1R03DA016696-01 (2003): $143500
Early Drug Exposure And Drug Reward Mechanisms
Susan L Andersen, Associate Professor
Mc Lean Hospital (belmont, Ma) 115 Mill St Belmont, Ma 02478
Grant 1R01DA015403-01A2 from National Institute On Drug Abuse IRG: IFCN
Abstract: Attention-deficit/hyperactivity disorder (ADHD) affects attention and motor capacities in approximately 6% of school-aged children, making it the most prevalent childhood disorder. ADHD can be treated effectively with stimulants including methylphenidate (MPH; RitalinTM), which are indirect dopamine (DA) agonists, and their use is rising. However, the use of such stimulants has been limited by concerns over their abuse or the possible role they play as a "gateway" to the abuse of other substances. Recent clinical data show that ADHD children treated with stimulants experience an 85% reduction in substance abuse compared with those who do not receive pharmacotherapy. The interpretation of these clinical observations, however, is difficult since effectively treated ADHD patients have improved psychosocial and academic skills that reduce other risk factors, such as social impairment. In addition, they do not address potential mechanisms leading to alternative interpretations including the possibility that early treatment with MPH can imprint on the underlying neurobiological substrate of stimulant abuse. In other words, juvenile exposure to MPH potentially can produce enduring effects on the neurobiology of the developing brain that outlast the period of drug treatment itself. Some of these questions can potentially be answered using animal models and it has been shown that chronic exposure to stimulant drugs, such as MPH, causes long-lasting increases in rewarding effects, thereby increasing vulnerability to substance abuse. However, these studies have been performed in adult animals limiting their interpretation for drug treatment in juvenile (developing) brains. We have, therefore, developed an animal model using MPH exposure in juvenile rats. In this model, MPH exposure made moderate doses of cocaine aversive and high doses less rewarding later in life demonstrating reduced vulnerability to stimulant abuse. Thus, our results indicate that imprinting and/or age differences in pharmacokinetics of MPH could mediate its enduring effects. In the proposed set of studies we endeavor to determine 1) the age-related contribution of bioavailability of MPH to cocaine reward later in life; 2) the effect of chronic MPH treatment on dopamine release in the pre-pubertal rat; 3) whether pre-pubertal exposure to MPH changes dopamine receptor expression; and 4) the role of dopamine in the underlying mechanism of MPH-induced changes in the pre-pubertal rat.
Keywords: attention deficit disorder, behavioral medicine, developmental neurobiology, dopamine agonist, drug abuse prevention, drug addiction antagonist, early experience, juvenile animal, methylphenidate, nonhuman therapy evaluation, pediatric pharmacology, pharmacokinetics, age difference, cocaine, dopamine receptor, drug administration rate /duration, receptor expression, behavioral /social science research tag, laboratory rat, outcomes research
Project start date: 2003-09-30
Project end date: 2008-06-30
1R01DA015403-01A2 (2003): $207629
Susan L Andersen
Mc Lean Hospital (belmont, Ma)
Project start date: 2011-01-01
Project end date: 2015-10-31
REPRESENTATIONS OF SIGNIFICANT OTHERS IN SOCIAL JUDGMENT
Susan L Andersen, Associate Professor
New York University Office Of Sponsored Programs New York, Ny 100122331
Grant 5R01MH048789-05 from National Institute Of Mental Health IRG: BSR
Project start date: 1992-03-01
Project end date: 1998-02-28
5R01MH048789-05 (1996): $116394