Cocaine-induced cardiovascular responses in rats during acute ethanol withdrawal.
The effects of cocaine administration during acute ethanol withdrawal on both the cardiovascular system and cocaine pharmacokinetics are unclear. This study demonstrated differences in the cardiovascular effects of i.v.-administered cocaine during acute ethanol withdrawal in awake, freely moving rats. The altered responses to cocaine while in acute ethanol withdrawal compared to control animals included: enhanced increases in mean arterial pressure and systemic vascular resistance, attenuated heart rate decreases, and enhanced cardiac index and stroke volume decreases. These results may suggest that acute ethanol withdrawal disrupts myocardial contractility when the myocardium is subjected to a large increase in blood pressure. Serial arterial blood sampling in additional groups of rats were done to assess plasma cocaine concentrations and to confirm the absence of ethanol in the blood. Plasma cocaine concentrations were not effected by acute ethanol withdrawal. These results indicate that the altered cardiovascular responses to cocaine during acute ethanol withdrawal were not a result of differences in cocaine plasma concentrations.
Briscoe
R J
RJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Baird
T J
TJ
Lerner
M R
MR
Brackett
D
D
Gauvin
D V
DV
D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000097:blood; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000097:blood / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D014662:Vasoconstrictor Agents; D000431:Ethanol; D003042:Cocaine