Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents.
BACKGROUND
Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats.


OBJECTIVE
The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis.


METHODS
The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D: -penicillamine (50 mg/kg, IP) on the plus maze.


RESULTS
SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol.


CONCLUSIONS
Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.
Correa
M
M
Area de Psicobiología, Universitat Jaume I, Campus Riu Sec, 12071 Castelló, Spain. correa@psb.uji.es
Manrique
H M
HM
Font
L
L
Escrig
M A
MA
Aragon
C M G
CM
D000079:Acetaldehyde / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D002374:Catalase / Q000037:antagonists & inhibitors; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003624:Darkness; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008027:Light; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D019810:Sodium Azide / Q000008:administration & dosage / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D000431:Ethanol; D019810:Sodium Azide; D002374:Catalase; D000079:Acetaldehyde; D000640:Amitrole