A program of research is proposed for studying behavioral effects of two types of drugs of major clinical, social , and theoretical important: 1) opioids, which have long represented a significant abuse problem; 2) caffeine, which is the most widely consumed behaviorally-active compound in the world, and which has many of the characteristics of a drug of abuse. The basic strategy of this research program is to use behavioral methodologies to study interactions of drugs with their neuronal substrates. The objective is to identify and characterize components of drug action that may be relevant to potential for abuse and to related phenomena, such as tolerance and physical dependence. The neuronal substrates of drug action will be characterized with receptor-selective agonists, antagonists, and tolerance and cross-tolerance. Representative compounds will be studied over a range of doses in several behavioral procedures, such as drug discrimination, food-reinforced operant responding, locomotor activity, and autotitration of reinforcement threshold for electrical brain stimulation. Experiments will be performed on rats and, often, on squirrel monkeys. This approach will help in assessing the generality of experimental findings with respect to pharmacological, behavioral, and species variables. The proposed experiments will address a number of hypotheses. Among these are: 1) Endogenous opioid peptides can modulate the behavioral effects of exogenously administered opioid drugs; 2) Similar components of drug action mediate discriminative stimulus, reinforcing stimulus, and subjective drug effects; 3) The discriminative stimulus effects of low and high doses of caffeine differ qualitatively from each other and reflect components of drug action that underlie, respectively, positive and negative mood states in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA000008-18
Application #
3075296
Study Section
Special Emphasis Panel (SRCD (45))
Project Start
1975-09-01
Project End
1995-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
18
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
White, David A; Michaels, Clifford C; Holtzman, Stephen G (2008) Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats. Pharmacol Biochem Behav 89:188-99
White, David A; Ballard, Michael E; Harmon, Alvin C et al. (2008) Acute delta- and kappa-opioid agonist pretreatment potentiates opioid antagonist-induced suppression of water consumption. Brain Res Bull 76:597-604
Michaels, Clifford C; Holtzman, Stephen G (2007) Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats. Pharmacol Biochem Behav 86:784-96
Michaels, Clifford C; Easterling, Keith W; Holtzman, Stephen G (2007) Maternal separation alters ICSS responding in adult male and female rats, but morphine and naltrexone have little affect on that behavior. Brain Res Bull 73:310-8
White, David A; Kalinichev, Mikhail; Holtzman, Stephen G (2007) Locomotor response to novelty as a predictor of reactivity to aversive stimuli in the rat. Brain Res 1149:141-8
Michaels, Clifford C; Holtzman, Stephen G (2006) Neonatal stress and litter composition alter sucrose intake in both rat dam and offspring. Physiol Behav 89:735-41
White, David A; Hwang, M Lisa; Holtzman, Stephen G (2005) Naltrexone-induced conditioned place aversion following a single dose of morphine in the rat. Pharmacol Biochem Behav 81:451-8
White, David A; Holtzman, Stephen G (2005) Periadolescent morphine exposure alters subsequent behavioral sensitivity to morphine in adult rats. Eur J Pharmacol 528:119-23
White, David A; Holtzman, Stephen G (2005) Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey: a further characterization. J Pharmacol Exp Ther 314:374-82
Jain, Raka; Holtzman, Stephen G (2005) Caffeine induces differential cross tolerance to the amphetamine-like discriminative stimulus effects of dopaminergic agonists. Brain Res Bull 65:415-21

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