Continuing research on this project is predicated on the assumption that valuable basic information, of long-term relevance both to drug abuse and more generally to understanding of neurotransmitter control of behavior, can be gotten from studies of similarities, differences, and interactions in the behavioral effects of drugs of abuse and of drugs affecting brain neurotransmitter activity. A primary focus will be on the development of a base of knowledge of the role of serotonin (5-HT) neurotransmission in the control and modulation of behavior, and of the participation of 5-HT systems in mediation of the action of certain drugs of abuse. Three general types of experiments will be done with schedule- controlled behavior of squirrel monkeys. One series of experiments will be concerned with the behavioral effects (including analgesic properties) of compounds with agonist and antagonist properties at the putative 5-HT-l and 5-HT-2 subtypes of the serotonin receptor. These compounds 1- naphthylpperazine (5-HT-l agonist, but 5-HT-2 antagonist); 1-(2- methoxyphenyl)piperazine (highly selective 5-HT-l agonist); and p- aminophenylethyl-m-TFMPP (a selective 5-HT-lA agonist). A second series of experiments will continue studies on the behavioral effects of the phenylisopropylamine hallucinogenic drugs 4-bromo-2,5-dimethoxyamphetamine (DOB) and 4-methyl- 2,5dimethoxyamphetamine (DOM), and will evaluate the extent to which the effects of these drugs can be blocked with antagonists of serotonin and of other neurotransmitters. Finally, experiments will be done to characterize interactions in the behavioral effects of opioid agonists and antagonists with hallucinogenic drugs such as DOM. Previous work in this laboratory and elsewhere has shown that the opioid antagonist naloxone markedly enhances the behavioral effects of hallucinogens, and there are suggestions that opioid agonists such as morphine have the opposite effect. In addition to morphine and naloxone, other drugs with differing affinities for the mu- and kappa-opioid receptor subtypes will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA001015-16
Application #
3206848
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1977-06-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
16
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
01545
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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