Modification of ethanol's reinforcing effectiveness in rhesus monkeys by cocaine, flunitrazepam, or gamma-hydroxybutyrate.
BACKGROUND
Although ethanol is frequently used in combination with other psychoactive drugs, the behavioral and pharmacological reasons for this form of polydrug abuse have not been well described.


METHODS
Rhesus monkeys with indwelling intravenous catheters produced intravenous injections of ethanol (50, 100, or 200 mg/kg/inj), flunitrazepam (0.001-0.03 mg/kg/inj), cocaine (0.01 or 0.03 mg/kg/inj), or combinations of ethanol and these drugs or gammahydroxybutyrate (GHB) (1.0 or 3.2 mg/kg/inj) by lever pressing according to a fixed-ratio schedule. The response requirement for each drug or drug combination was increased across sessions (10, 32, 100, 320, or 1,000). The dependent variables were rates of responding maintained by the drug or drug combination and the elasticity of drug demand when consumption was expressed as a function of price.


RESULTS
Elasticity (P (max)) values for each drug varied among the monkeys but retained the same rank order for the monkeys, suggesting a fundamental difference in the animals' apparent sensitivities to the reinforcing effects of the drugs. Combining ethanol with the other drugs did not increase their reinforcing effectiveness. GHB (ineffective in previous studies) did not modify ethanol's reinforcing effects; demand functions for the combination of ethanol and flunitrazepam were slightly less elastic than for ethanol alone, but no different from that for flunitrazepam alone; adding ethanol to cocaine detracted from the reinforcing effectiveness of cocaine.


CONCLUSIONS
The hypothesis that use of ethanol in combination with sedative and stimulant drugs is due to an ability of ethanol to enhance the reinforcing effects of these drugs is not supported.
Winger
Gail
G
Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA. gwinger@umich.edu
Galuska
Chad M
CM
Hursh
Steven R
SR
D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005445:Flunitrazepam / Q000008:administration & dosage / Q000494:pharmacology; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012646:Self Administration; D012978:Sodium Oxybate / Q000008:administration & dosage / Q000494:pharmacology; D019966:Substance-Related Disorders
D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D018757:GABA Modulators; D000431:Ethanol; D005445:Flunitrazepam; D012978:Sodium Oxybate; D003042:Cocaine