This competing continuation of K05DA17918 is submitted in response to PA-09-076 and requests 5 additional years of support to provide protected time for the PI to continue a successful preclinical research program on the behavioral pharmacology of opioids and other drugs and to mentor students and other young investigators in the area of drug abuse. Progress on the original aims of this grant was as follows: 1) increased NIH support for the PI, his mentees, and collaborators;2) made significant progress in research projects on the behavioral pharmacology of opioids and other drugs of abuse;3) significantly increased drug abuse research and training activities at UTHSCSA;4) led the effort to expand and renovate animal facilities for behavioral research on drug abuse;and 5) contributed to the successful career development of student and junior faculty mentees. The current grant comprises 5 specific aims.
Aim 1 continues a 23-year research program on opioid dependence and withdrawal with a new focus on drug combinations.
Aim 2 builds on compelling new data showing that chronic opioid treatment and its discontinuation dramatically alter delay discounting, an often used measure of an important aspect of impulsivity, delay discounting.
Aim 3 continues and expands a successful collaboration with several investigators and explores the effects of food restriction and of eating high fat food on behavioral, neurochemical, and other effects of drugs acting on serotonin and dopamine systems.
Aim 4 continues an active mentoring program (>25% effort) of students and young investigators, and Aim 5 promotes further growth in drug abuse research and training activities at UTHSCSA, including preparation of T32 and multi-investigator research applications. Prior support under the K mechanism has allowed the PI to continue and expand his research efforts as well as the research programs of his collaborators. Continued support under this K award will allow the PI to devote at least 75% of his effort to research and mentoring in drug abuse.

Public Health Relevance

Despite the importance of opioids for treating pain, they are not effective in many patients, and their clinical use is limited by concerns about abuse and dependence;while impulsivity and drug abuse often covary, it is not clear whether impulsivity is a risk or cause of drug abuse and little is known about how drug use, especially chronic drug use, impacts impulsivity. Food and drugs can affect the same reward mechanism in brain, although the impact of feeding conditions on drug effects is poorly understood. Research conducted under this Senior Scientist Award examines three different drug abuse related questions: 1) can drugs of abuse that are used to treat pain be taken together without increasing their abuse;2) can drugs of abuse increase impulsivity when they are taken or when they are no longer taken;and 3) can drugs of abuse have effects that depend on how much and what you eat?

Agency
National Institute of Health (NIH)
Type
Research Scientist Award (K05)
Project #
5K05DA017918-10
Application #
8719071
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Lynch, Minda
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Health Science Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Serafine, Katherine M; Bentley, Todd A; Koek, Wouter et al. (2015) Eating high fat chow, but not drinking sucrose or saccharin, enhances the development of sensitization to the locomotor effects of cocaine in adolescent female rats. Behav Pharmacol 26:321-5
Baladi, Michelle G; Newman, Amy H; France, Charles P (2014) Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats. Psychopharmacology (Berl) 231:581-91
Collins, Gregory T; Jackson, Jonathan A; Koek, Wouter et al. (2014) Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate cocaine from saline: influence of feeding condition. Eur J Pharmacol 729:123-31
Serafine, Katherine M; France, Charles P (2014) Restricted access to standard or high fat chow alters sensitivity of rats to the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane. Behav Pharmacol 25:44-52
Maguire, David R; France, Charles P (2014) Impact of efficacy at the ?-opioid receptor on antinociceptive effects of combinations of ?-opioid receptor agonists and cannabinoid receptor agonists. J Pharmacol Exp Ther 351:383-9
Serafine, Katherine M; Bentley, Todd A; Grenier, Amandine E et al. (2014) Eating high fat chow and the behavioral effects of direct-acting and indirect-acting dopamine receptor agonists in female rats. Behav Pharmacol 25:287-95
Gerak, Lisa R; France, Charles P (2014) Discriminative stimulus effects of pregnanolone in rhesus monkeys. Psychopharmacology (Berl) 231:181-90
Zanettini, Claudio; France, Charles P; Gerak, Lisa R (2014) Quantitative pharmacological analyses of the interaction between flumazenil and midazolam in monkeys discriminating midazolam: Determination of the functional half life of flumazenil. Eur J Pharmacol 723:405-9
Maguire, David R; Henson, Cedric; France, Charles P (2014) Effects of amphetamine on delay discounting in rats depend upon the manner in which delay is varied. Neuropharmacology 87:173-9
Tanno, Takayuki; Maguire, David R; Henson, Cedric et al. (2014) Effects of amphetamine and methylphenidate on delay discounting in rats: interactions with order of delay presentation. Psychopharmacology (Berl) 231:85-95

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