Simultaneous cocaine exposure abolishes ethanol tolerance.
We measured changes in locomotor impairment in rats caused by ethanol exposure either given alone or simultaneously with cocaine. An initial ethanol injection (2.1 g/kg, intraperitoneally (i.p.) disrupted rotorod performance and this disruption was not significantly affected by the cocaine injection (15 mg/kg, i.p.). After 13 daily drug treatments, performance in the ethanol group was significantly improved whereas in the cocaine+ethanol group, performance remained disrupted to the same extent throughout testing (49 +/- 14 min). Cocaine sensitization developed after repeated exposure and this sensitization was greater in the cocaine+ethanol group. Next, all groups were tested with simultaneous ethanol and cocaine. Tolerance was not diminished in the ethanol group, whereas groups receiving saline, cocaine, or cocaine+ethanol exhibited equally disrupted behavior. During an ethanol-only test, the cocaine+ethanol group also did not respond differently from groups receiving saline or cocaine alone. There was no difference in tolerance of the GABAA receptor to ethanol enhancement in cortical microsacs from the ethanol and cocaine+ethanol groups, nor did cocaine affect blood ethanol levels after initial or repeated exposure. A non-sensitizing dose of cocaine (7.5 mg/kg, i.p.) had no effect on the development or expression of ethanol tolerance. Cocaine disruption of ethanol tolerance thus appears to be partly due to interference of expression of ethanol tolerance by cocaine sensitization and partly due to inhibition of the development of ethanol tolerance by non-GABAergic mechanisms.
Peris
J
J
University of Florida, Department of Pharmacodynamics, Gainesville 32610, USA.
Sealey
S A
SA
Jung
B J
BJ
Gridley
K E
KE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects*
D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D018079:Receptors, GABA; D000431:Ethanol; D003042:Cocaine