Diazepam fails to potentiate GABA-induced chloride uptake and to produce anxiolytic-like action in aged rats

The pharmacological response to benzodiazepines has been demonstrated to be different in aged individuals in comparison to adults. We studied the age- dependent changes in some of the in vitro and behavioral effects of diazepa m in aged (24 months old) rats, comparing them to adults (3 months old). We evaluated the in vitro gamma -aminobutyric acid (GABA)-induced Cl-36(-) up take and the diazepam potentiation of GABA-stimulated Cl-36(-) uptake in mi crosacs from cerebral cortex of both groups of animals. We found no differe nces in the GABA-stimulated Cl-36(-) uptake between adult and aged animals, and diazepam failed to potentiate GABA-induced Cl-36(-) flux in the aged c ortical microsacs. We also examined the effect of 0.03-10 mg of diazepam on locomotor activity in an open-field test and the anxiolytic-like action of diazepam in doses ranging from 0.03 to 1 in a dark-light transition test. We observed no anxiolytic-like action of the drug in the dark-light transit ion test in the aged rats, while there was a shift to the left in the dimin ution of locomotor activity evaluated by the open-field test. We conclude t hat the pharmacodynamic changes observed in cortical GABAA receptors in age d rats could partially explain the lack of anxiolytic-like action but not t he oversedation evidenced in this group of animals. (C) 2001 Elsevier Scien ce Inc. All rights reserved.