The aim of the proposed research is to assess the neuronal mechanisms underlying certain behavioral effects of indole- and phenylalkylamine hallucinogens (e.g., LSD [d-lysergic acid diethylamide] and mescaline [3,4,5-trimethoxyphenylthylamine]), central nervous system (CNS) stimulants (e.g., d-amphetamine and cocaine) and the so-called """"""""designer"""""""" drugs, MDA (3,4-methylenedioxyamphetamine) and MDMA (3,4- methylenedioxymethamphetamine), which appear to have both hallucinogenic and stimulant properties. Our principle behavioral procedure will continue to be drug discrimination which has been of considerable value in advancing our understanding of drug actions and has served as an excellent, if not unique animal model of the subjective effects of hallucinogenic and related substances in humans. The reasons we continue to use this admittedly difficult and time-consuming assay include the fact that it is pharmacologically specific in that substitution of a novel compound for a training drug (generalization of a drug """"""""cue"""""""") usually reflects common mechanisms of action rather than simply psychoactive effects and blockade of the stimulus properties of a training or test drug (during a combination test) normally requires that the """"""""agonist"""""""" and """"""""antagonist"""""""" compounds have similar receptor actions. In addition, drug discrimination is sensitive in that it is able to reliably assess the behavioral effects of very small doses of drugs such as LSD and lisuride and reliable, possibly because it uses response choice rather than rate as its primary dependent variable and thereby avoids confounds caused by unconditioned effects of test or training drugs on motor behavior. Finally, drug discrimination results correlate highly with neurochemical (e.g., receptor binding) results; thus, this procedure has acquired respectability as a pharmacological assay by confirming behavioral (in vivo) relevance to in vitro or ex vivo findings.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002543-18
Application #
3207410
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1980-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
18
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Arts and Sciences
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Appel, James B; West, William B; Buggy, James (2004) LSD, 5-HT (serotonin), and the evolution of a behavioral assay. Neurosci Biobehav Rev 27:693-701
Appel, J B; West, W B; Rolandi, W G et al. (1999) Increasing the selectivity of drug discrimination procedures. Pharmacol Biochem Behav 64:353-8
Van Groll, B J; Appel, J B (1992) Stimulus effects of d-amphetamine 1: DA mechanisms. Pharmacol Biochem Behav 43:967-73
Callahan, P M; Appel, J B; Cunningham, K A (1991) Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. Psychopharmacology (Berl) 103:50-5
Appel, J B; Baker, L E; Barrett, R L et al. (1991) Use of drug discrimination in drug abuse research. NIDA Res Monogr :369-97
Callahan, P M; Appel, J B (1990) Differentiation between the stimulus effects of (+)-lysergic acid diethylamide and lisuride using a three-choice, drug discrimination procedure. Psychopharmacology (Berl) 100:13-8
Appel, J B; Callahan, P M (1989) Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline. Eur J Pharmacol 159:41-6
Barrett, R L; Appel, J B (1989) Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine. Psychopharmacology (Berl) 99:13-6
Callahan, P M; Appel, J B (1988) Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4- methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline. J Pharmacol Exp Ther 246:866-70
Appel, J B; Weathersby, R T; Cunningham, K A et al. (1988) Stimulus properties of dopaminergic drugs: comparisons involving selective agonists and antagonists. Psychopharmacol Ser 4:44-56

Showing the most recent 10 out of 23 publications