This project uses monkeys with chronically indwelling intravenous catheters that can be used for passive drug administration, active drug self-administration and to take blood samples. When blood samples are taken, they will be analyzed for ACTH and cortisol levels. The goals of this project are first to determine the effects of acute administration of opioid drugs on the HPA axis, and to determine if increases in HPA axis activity can be used to measure acute naloxone-precipitated dependence to mu and kappa opioids. If so, the parameters of time following drug administration and the interval between drug injections will be evaluated to determine the role they play in the development of acute dependence. Second, the ability of breathing 5 percent CO2 and administration of 13 carboline ethyl ester to provoke a stress response as indicated by increases in ACTH will be measured. The ability of morphine and diazepam to attenuate each of these stress responses will be determined and compared. Morphine dependence will be produced in these animals and evidence for protracted abstinence will be looked for as a hyporeactivity of the HPA axis to 5 percent CO2 and 13CCE administration. Such a protracted abstinence reaction to restraint stress has been demonstrated in rats. The effects of self-administered opioids on the HPA axis will be established and compared with the effects previously observed with passive opioid administration. These effects of self-administered opioids on plasma levels of ACTH and cortisol will also be determined in animals with high """"""""basal"""""""" levels of ACTH and cortisol as a result of either presession administration of 13CCE or opioid withdrawal. A procedure whereby demand functions are obtained in single 2-hr sessions will be used to determine if the elasticity of the demand function for short-acting opioid is decreased during opioid withdrawal. Finally, evaluation of the reinforcing effects of novel opioids as submitted by government agencies, academic, or industrial laboratories will continue.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA000254-31
Application #
6647294
Study Section
Special Emphasis Panel (ZDA1)
Project Start
2002-08-15
Project End
2003-06-30
Budget Start
Budget End
Support Year
31
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Moses, Tabitha E H; Lundahl, Leslie H; Greenwald, Mark K (2018) Factors associated with sedative use and misuse among heroin users. Drug Alcohol Depend 185:10-16
Reilly, Mark P; Berndt, Sonja I; Woods, James H (2016) On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta). Behav Anal (Wash D C) 16:200-209
Woodcock, Eric A; Lundahl, Leslie H; Stoltman, Jonathan J K et al. (2015) Progression to regular heroin use: examination of patterns, predictors, and consequences. Addict Behav 45:287-93
Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J et al. (2015) Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence. Exp Clin Psychopharmacol 23:455-63
Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J et al. (2015) Exploration of the telescoping effect among not-in-treatment, intensive heroin-using research volunteers. Drug Alcohol Depend 148:217-20
Mancha, Brent Edward; Hulbert, Alicia; Latimer, William W (2012) A latent class analysis of alcohol abuse and dependence symptoms among Puerto Rican youth. Subst Use Misuse 47:429-41
Moynihan, Humphrey A; Derrick, Ian; Broadbear, Jillian H et al. (2012) Fumaroylamino-4,5-epoxymorphinans and related opioids with irreversible ? opioid receptor antagonist effects. J Med Chem 55:9868-74
Mancha, Brent E; Rojas, Vanessa C; Latimer, William W (2012) Alcohol use, alcohol problems, and problem behavior engagement among students at two schools in northern Mexico. Alcohol 46:695-701
Pichika, Rama; Jewett, Douglas M; Sherman, Philip S et al. (2010) Synthesis and in vivo brain distribution of carbon-11-labeled ?-opioid receptor agonists. Nucl Med Biol 37:989-96
Cooper, Ziva D; Shi, Yong-Gong; Woods, James H (2010) Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats. Psychopharmacology (Berl) 212:369-78

Showing the most recent 10 out of 22 publications