The research proposed is designed to provide a more quantitative measure of the effects of opioid agonists, antagonists, and mixed agonist-antagonists on both mu- and kappa-induced opioid dependence in rhesus monkeys and pigeons. In monkeys, much data has been accumulated on this issue using observations of behavioral changes following administration of opioids in morphine- and U-50,488- (a kappa agonist) dependent subjects. This procedure has several drawbacks, including dependence on trained observers, subjective reports of withdrawal signs, use of rating scales, and the need for high morphine doses to produce strong dependence. In the current proposal, monkeys will be trained to discriminate the administration of naltrexone from that of saline using a standard drug discrimination procedure. Naltrexone will serve as an indicator of morphine withdrawal in a group of monkeys receiving relatively low doses of morphine chronically during training and testing of the naltrexone cue, and will serve as an indicator of U-50,488 withdrawal in a group of monkeys receiving chronic U-50,488 during this time. The capacity of this procedure to produce data relevant to the modification of withdrawal has been demonstrated well by prior studies in pigeons. Pigeons will be trained to discriminate naltrexone from both morphine and saline to allow parametric evaluation of the effects of drugs on withdrawal from each of three different morphine maintenance doses. These series of studies should be helpful in assessing drugs for potential use in the treatment of opioid dependence, for assisting in the classification of currently available and newly developed opiate analgesics, as well as having considerable interest to basic scientists in the field of opioid pharmacology and behavioral pharmacology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA005018-01
Application #
3210960
Study Section
(SRCD)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Collins, Gregory T; Gerak, Lisa R; France, Charles P (2018) The behavioral pharmacology and therapeutic potential of lorcaserin for substance use disorders. Neuropharmacology 142:63-71
Gerak, Lisa R; Collins, Gregory T; Maguire, David R et al. (2018) Effects of lorcaserin on reinstatement of responding previously maintained by cocaine or remifentanil in rhesus monkeys. Exp Clin Psychopharmacol :
Minervini, Vanessa; France, Charles P (2018) Effects of morphine/CP55940 mixtures on an impulsive choice task in rhesus monkeys. Behav Pharmacol 29:60-70
Gerak, Lisa R; Maguire, David R; Woods, James H et al. (2018) Reversal and prevention of the respiratory-depressant effects of heroin by the novel ยต opioid receptor antagonist methocinnamox in rhesus monkeys. J Pharmacol Exp Ther :
Weed, Peter F; Gerak, Lisa R; France, Charles P (2018) Ventilatory-depressant effects of opioids alone and in combination with cannabinoids in rhesus monkeys. Eur J Pharmacol 833:94-99
Maguire, David R; France, Charles P (2018) Reinforcing effects of opioid/cannabinoid mixtures in rhesus monkeys responding under a food/drug choice procedure. Psychopharmacology (Berl) 235:2357-2365
Weed, Peter F; France, Charles P; Gerak, Lisa R (2017) Preference for an Opioid/Benzodiazepine Mixture over an Opioid Alone Using a Concurrent Choice Procedure in Rhesus Monkeys. J Pharmacol Exp Ther 362:59-66
Maguire, David R; Gerak, Lisa R; France, Charles P (2016) Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Behav Pharmacol 27:155-64
Gerak, L R; France, C P (2016) Combined Treatment with Morphine and ?9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal. J Pharmacol Exp Ther 357:357-66
Maguire, David R; France, Charles P (2016) Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys. Behav Pharmacol 27:249-57

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