The objective of this K05 application is to obtain salary support for release time from teaching and administrative duties not directly related to research. This would increase time allocated to research from 40% before the K05 to 75-90. An overview of the candidate's 31-year background in drug abuse research is provided including a list of publications, presentations, a citation analysis, research funding, and mentorship of students, science advocacy, and educational activities. Short-and-long-term research plans that will be implemented with released time are discussed. Specific activities planned to sustain outstanding research performance, blending of past and future goals, the likelihood of continuing successful contributions, and plans to obtain and provide instruction on the responsible conduct of science are also discussed. A progress report describes accomplishments made in the first 4 years of this K05 award 2002-2006. The research plan consists of 2 continuing R01 projects that have been funded by NIDA for over 20 years, a new R01 (PI) that is under review, and a P20 application (Co-Pi) that is under review. The first grant is a nonhuman primate model to study sex, phase of menstrual cycle, and impulsivity as factors that affect the Vulnerability to drug abuse and to implement innovative behavioral and pharmacological treatments for drug abuse. The overall hypothesis is that these vulnerability factors will predict reinforcing efficacy and treatment success. The second grant will examine behavioral and pharmacological interventions in rats selected for several vulnerable behaviors. These factors will be compared during critical transition phases of addiction, acquisition, escalation, and reinstatement. The hypothesis is that a predisposition (individual differences) for excessive behavior directed toward novel and rewarding nondrug activities increases vulnerability to drug abuse and responsiveness to treatment. The third proposed grant, to be conducted in adolescent rats, is focused on factors underlying drug abuse. The overall hypothesis is that adolescent animals are more impulsive and susceptible to hormonal influences on drug seeking behavior than adults. The fourth proposed grant, a P20, would consist of an animal project that will parallel and inform two human projects involving cocaine abusers and college students varying in impulsive behavior. The basic theme is how, impulsivity is related to drug abuse, and MR imaging will be used in rats and monkeys to compare neurobiological and behavioral phenotypes. Species, gender, several drugs of abuse, routes of administration, and phases of addiction will be compared. The results will allow for identification of biological, behavioral, and environmental factors leading to recognition of individuals at risk for drug abuse, and the experimental interventions used with these models will inform prevention and treatment strategies for humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA015267-09
Application #
7802053
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wetherington, Cora Lee
Project Start
2002-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$138,988
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Psychiatry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Carroll, Marilyn E; Lynch, Wendy J (2016) How to study sex differences in addiction using animal models. Addict Biol 21:1007-29
Radke, Anna K; Zlebnik, Natalie E; Carroll, Marilyn E (2015) Cocaine withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake. Pharmacol Biochem Behav 129:51-5
Zlebnik, Natalie E; Carroll, Marilyn E (2015) Prevention of the incubation of cocaine seeking by aerobic exercise in female rats. Psychopharmacology (Berl) 232:3507-13
Holtz, Nathan A; Carroll, Marilyn E (2015) Cocaine self-administration punished by intravenous histamine in adolescent and adult rats. Behav Pharmacol 26:393-7
Zlebnik, Natalie E; Carroll, Marilyn E (2015) Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity. Psychopharmacology (Berl) 232:1049-59
Holtz, Nathan A; Radke, Anna K; Zlebnik, Natalie E et al. (2015) Intracranial self-stimulation reward thresholds during morphine withdrawal in rats bred for high (HiS) and low (LoS) saccharin intake. Brain Res 1602:119-26
Regier, Paul S; Claxton, Alexander B; Zlebnik, Natalie E et al. (2014) Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low impulsive rats: treatment with allopregnanolone. Drug Alcohol Depend 143:58-64
Zlebnik, Natalie E; Saykao, Amy T; Carroll, Marilyn E (2014) Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats. Psychopharmacology (Berl) 231:3787-98
Zlebnik, Natalie E; Hedges, Valerie L; Carroll, Marilyn E et al. (2014) Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats. Behav Brain Res 261:71-8
Holtz, Nathan A; Anker, Justin J; Regier, Paul S et al. (2013) Cocaine self-administration punished by i.v. histamine in rat models of high and low drug abuse vulnerability: effects of saccharin preference, impulsivity, and sex. Physiol Behav 122:32-8

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