Blockade of adenosine and dopamine receptors inhibits the development of rapid tolerance to ethanol in mice.
BACKGROUND
Several reports have suggested the involvement of brain adenosine and dopamine receptors in different actions produced by ethanol such as motor incoordination or anxiolytic, hypnotic and reinforcing effects. The co-localization and interaction between adenosine and dopamine receptors in different brain regions has also been well documented. However, few studies have demonstrated the involvement of these mechanisms in the tolerance induced by ethanol.


OBJECTIVE
The aim of the present study was to evaluate the role of adenosine and dopamine receptors in the development of rapid tolerance to ethanol-induced motor incoordination in mice.


METHODS
In connection with the rota-rod apparatus, the effects of acute administration of the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A1 receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A2A receptor antagonist), together with R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390, dopamine D1 receptor antagonist) and sulpiride (dopamine D2 receptor antagonist), alone or in combination with ethanol (2.25 g/kg, i.p.), were studied. Twenty-four hours after, all animals were re-tested on the rota-rod after receiving the same dose of ethanol.


RESULTS
The repeated administration of ethanol promoted a significant reduction of motor impairment on day 2 (i.e. rapid tolerance). This effect was blocked by caffeine (3.0-30.0 mg/kg, i.p.), DPCPX (3.0-6.0 mg/kg, i.p.) or SCH23390 (0.01-0.03 mg/kg, s.c.), but not with ZM241385 (0.5-1.0 mg/kg, i.p.) or sulpiride (1.0-3.0 mg/kg, i.p.).


CONCLUSIONS
Our results suggest that the rapid tolerance to ethanol-induced motor impairment in mice may be modulated by adenosine A1 receptors and dopamine D1 receptors.
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Trindade, 88049-900, Florianópolis, SC, Brazil.
Luciano C
LC
Batista
Rui D S
RD
Prediger
Gina S
GS
Morato
Reinaldo N
RN
Takahashi
D000818:Animals; D001921:Brain / Q000187:drug effects; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D058915:Purinergic P1 Receptor Antagonists; D011954:Receptors, Dopamine / Q000187:drug effects*
D058915:Purinergic P1 Receptor Antagonists; D011954:Receptors, Dopamine; D000431:Ethanol