Anxiolytic effects of ethanol and phenobarbital are abolished in test-experienced rats submitted to the elevated plus maze.
Prior test experience compromises the anxiolytic efficacy of benzodiazepines (BZs) either in rats or mice, a phenomenon not exclusive to the elevated plus-maze (EPM) animal model of anxiety, which is referred to as "one-trial tolerance." However, it remains to be determined whether a similar event occurs when testing other drugs that also possess binding-sites on the GABA(A) receptor, such as ethanol and barbiturates. In the present study, we have addressed this issue using maze-naive and maze-experienced (free exploration of the EPM 48 h earlier for 5 min) rats pretreated with ethanol (1.0-1.4 g/kg) or phenobarbital (20-60 mg/kg) and submitted to the EPM. The results confirmed the anxiolytic profile of both drugs, represented by increased open arm exploration and decreased risk assessment behavior, in maze-naive rats. However, in maze-experienced rats, neither ethanol nor phenobarbital anxiolytic effects were observed, suggesting that prior maze experience compromised the drugs' anxiolytic activity. Thus, the "one-trial tolerance" phenomenon might also be extended to other drugs that bind to the GABA(A) receptor complex.
Bertoglio
L J
LJ
Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, Florianópolis, SC 88015-420, Brazil.
Carobrez
A P
AP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D000431:Ethanol; D010634:Phenobarbital