ANTICONFLICT EFFECT OF ALPIDEM AS COMPARED WITH THE BENZODIAZEPINE ALPRAZOLAM IN RATS

A comparative study between two drugs acting on the GABA(A) receptor, alprazolam and alpidem was undertaken, using simple tests such as meas urement of spontaneous locomotor activity, four plates test and rotaro d in mice. Additional conflict test was further performed using a new conflict paradigm where the opportunity existed for rats to choose dur ing punished periods between immediate, punished reinforcement and del ayed non-punished reinforcement. The benzodiazepine alprazolam, demons trated, as expected, strong anxiolytic effects in mice and increased p unished response in rats at non sedative doses (0.5, 1 mg/kg). High do ses of alprazolam decreased spontaneous locomotor activity and induced myorelaxant effects in mice. Alpidem, an imidazopyridine derivative, induced motor impairment in mice and only very weak anxiolytic effects in the four plates test in mice (4 mg/kg) and in punished procedure i n rats (32 mg/kg). As alprazolam is a full agonist for the GABA(A) rec eptor complex and alpidem is a partial agonist acting with specificity on omega 1 GABA(A) receptor subtypes, the results are discussed. Acti vity on omega 1 receptor subtypes is perhaps not sufficient in order t o obtain a true anti-conflict effect and compounds such as alpidem onl y relieve some of the symptoms of anxiety disorders. Copyright (C) 199 7 Elsevier Science Inc.