The overall aims of this project are to characterize certain of the behavioral effects of representative opioid drugs, to compare these effects with similar actions of drugs of other classes (alpha2-adrenoreceptor agonists, serotonin agonists, and histamine H1 antagonists), and to identify significant interactions in the behavioral effects of these drugs. A working hypothesis of the project is that valuable basic information, relevant both to drug abuse and to fuller understanding of neurotransmitter participation in the control of behavior, will come from work of this nature. Three general types of experiments will be done. First, because certain of the behavioral effects of acutely administered opioids, alpha2 agonists such as clonidine, and serotonin agonists are similar, one series of experiments will determine the extent to which tolerance to the behavioral effects of one of these drugs is transferred to drugs of the other two classes (cross-tolerance). In these and other experiments, responding under various schedules of reinforcement and under electrical-stimulus titration procedures will be studied in rats and squirrel monkeys. A second series of experiments will focus on behavioral sequelae of changes in CNS serotonin activity, and the possible role such changes might play in mediation of the behavioral effects of opioid drugs. There will also be studies of the possible role of dopamine in mediation of certain of the behavioral effects of serotonin agonist drugs. A final series of experiments will focus on the behavioral effects of histamine H1 antagonists, given both alone and in combination with opioid drugs. Drugs of this class are among the most widely taken, generally under minimal medical supervision, and there are recent reports of significant interactions in the effects of antihistamines and opioid drugs both in experimental animals and humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA001015-12
Application #
3206843
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1977-06-01
Project End
1988-06-30
Budget Start
1985-08-01
Budget End
1986-06-30
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
McKearney, J W (1990) Effects of serotonin agonists on operant behavior in the squirrel monkey: quipazine, MK-212, trifluoromethylphenylpiperazine, and chlorophenylpiperazine. Pharmacol Biochem Behav 35:181-5
McKearney, J W (1989) Serotonin-antagonist effects of 1-(1-naphthyl)piperazine on operant behavior of squirrel monkeys. Neuropharmacology 28:817-21
McKearney, J W (1989) Apparent antinociceptive properties of piperazine-type serotonin agonists: trifluoromethylphenylpiperazine, chlorophenylpiperazine, and MK-212. Pharmacol Biochem Behav 32:657-60
McKearney, J W (1988) Variability in the effects of 4-bromo-2,5-dimethoxyamphetamine (DOB) on operant behavior of squirrel monkeys. Pharmacol Biochem Behav 29:281-5
Smith, J B (1987) Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol. Psychopharmacology (Berl) 91:127-30
Smith, J B (1986) Effects of fixed-ratio length on the development of tolerance to decreased responding by l-nantradol. Psychopharmacology (Berl) 90:259-62
Smith, J B (1986) Effects of chronically administered d-amphetamine on spaced responding maintained under multiple and single-component schedules. Psychopharmacology (Berl) 88:296-300
Carlson, K R; Cooper, D O (1985) Morphine dependence and protracted abstinence: regional alterations in CNS radioligand binding. Pharmacol Biochem Behav 23:1059-63
McKearney, J W (1985) Tolerance to behavioral effects of clonidine after chronic administration of morphine. Pharmacol Biochem Behav 22:573-6
McKearney, J W (1985) Relative potencies of histamine H1 antagonists as behavioral stimulants in the squirrel monkey. Psychopharmacology (Berl) 86:380-1

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