The aims are to explore behavioral effects of some abused drug mixtures, to use recently developed methods to analyze discriminative effects of single drugs with multiple effects, and to explore the potential of Occasion Setting in relation to drug action. Both mixtures of drugs and single substances with multiple effects will be analyzed as compound interoceptive stimuli, bringing to drug action the theoretical framework of associative learning that is more commonly used in studies of compound exteroceptive stimuli. The emphasis will be upon mixtures of which one component is an opioid, notably mixtures of heroin plus cocaine (""""""""speedballs"""""""") and of pentazocine plus tripelennamine (""""""""T's & blues""""""""). Experiments will use methods developed previously in the project: [1] the AND-discrimination procedure will provide sensitive measures for detecting interactions between drugs in mixtures and [2] the AND-OR discrimination procedure will be used to enhance the pharmacological specificity of stimuli produced by mixtures. The first experiments on Occasion Setting with drugs in two-lever paradigms will be carried out. The specificity of discriminative stimuli produced by mixtures of abused substances such as heroin plus cocaine will be evaluated in tests with pharmacologically similar drugs and drug mixtures, and with compounds from other pharmacological classes. Similarities and differences between different abused and non-abused mixtures will be determined to identify the key drug actions responsible for the characteristic effects of the mixtures. These techniques will be used to analyze in greater depth than previously the discriminative effects of single opioid drugs with multiple effects; the mixed agonist-antagonist opioids cyclazocine, pentazocine, buprenorphine and butorphanol may produce their characteristic effects and patterns of abuse through different profiles of effects across m- and k-opioid, NMDA and s receptors. Cyclazocine will be a reference drug and experiments with it will be primarily to standardize methods; the other mixed agonist-antagonists have different, less well-understood effects and neuropharmacological actions, but are of greater present-day clinical significance. Profiles of effects of these drugs will be examined for their intrinsic importance and to inform studies on their actions in mixtures with tripelennamine and cocaine.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005543-12
Application #
6175111
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lynch, Minda
Project Start
1988-09-01
Project End
2002-09-30
Budget Start
2000-04-01
Budget End
2002-09-30
Support Year
12
Fiscal Year
2000
Total Cost
$107,519
Indirect Cost
Name
University of London Institute of Psychiatry
Department
Type
DUNS #
City
London
State
Country
United Kingdom
Zip Code
Stolerman, I P; Mariathasan, E A (2003) Nicotine trace discrimination in rats with midazolam as a mediating stimulus. Behav Pharmacol 14:55-66
Stolerman, I P; Childs, E; Hahn, B et al. (2002) Drug trace discrimination with nicotine and morphine in rats. Behav Pharmacol 13:49-58
Stolerman, I P; Olufsen, K S (2000) Influence of training history on ethanol discrimination in rats. Behav Pharmacol 11:603-12
Stolerman, I P; Mariathasan, E A; White, J A (1999) Influencing the specificity of drug mixture discriminations by varying the training procedure. Behav Pharmacol 10:657-64
Mariathasan, E A; Stolerman, I P (1994) Functional relationships, previous history and the discrimination of a drug mixture in rats. Drug Alcohol Depend 35:117-25
Mariathasan, E A; Stolerman, I P (1992) Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Psychopharmacology (Berl) 109:99-106
Marston, H M; Garcha, H S; Robbins, T W et al. (1992) Drug discrimination learning in rats with excitotoxic lesions of nucleus basalis and ventral globus pallidus. Behav Brain Res 51:93-102
Stolerman, I P; Mariathasan, E A; Garcha, H S (1991) Discriminative stimulus effects of drug mixtures in rats. NIDA Res Monogr :277-306
Stolerman, I P; Mariathasan, E A (1990) Discrimination of an amphetamine-pentobarbitone mixture by rats in an AND-OR paradigm. Psychopharmacology (Berl) 102:557-60