The interaction of dopamine, cocaine, and cocaethylene with ethanol on central nervous system depression in mice.
The interactions between dopamine, cocaine, cocaethylene, and ethanol were studied in Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measure of CNS depression. Animals were injected intraperitoneally (IP) with ethanol (4.0 g/kg). which caused a LORR. Immediately upon regaining of the righting reflex, mice were injected intracerebroventricularly (ICV) with saline, dopamine (0.1, 0.5, or 1.0 mumol/kg), cocaine (1, 15, or 25 mumol/kg), or cocaethylene (1, 15, or 25 mumol/kg). In the presence of systemic ethanol, all three compounds produced CNS depression in a dose-dependent manner. The dopamine D2-receptor antagonist sulpiride and the D1-receptor antagonist fluphenazine were given acutely ICV with dopamine in the presence of systemic ethanol to examine whether these antagonists could block the return to the LORR produced by dopamine. Sulpiride, however, actually enhanced the interaction between ethanol and dopamine in a dose-dependent manner as measured by the LORR; fluphenazine neither blocked nor enhanced the effect of dopamine in the presence of systemic ethanol. In addition, these antagonists had no effect on cocaine- and cocaethylene-induced CNS depression in the presence of systemic ethanol. The results of this study showed that the neurotransmitter dopamine and both cocaine and cocaethylene can promote further CNS depression in the presence of systemic ethanol, and that dopamine was significantly more potent than cocaine and cocaethylene as measured by the return to the LORR.
Wilson
D M
DM
Department of Pharmacology, School of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
Ferko
A P
AP
Barbieri
E J
EJ
DiGregorio
G J
GJ
Bobyock
E
E
McMichael
R
R
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005476:Fluphenazine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013469:Sulpiride / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D000431:Ethanol; D013469:Sulpiride; C066444:cocaethylene; D003042:Cocaine; D005476:Fluphenazine; D004298:Dopamine