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

Abstract

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 diazepam in aged (24 months old) rats, comparing them to adults (3 months old). We evaluated the in vitro γ-aminobutyric acid (GABA)-induced 36Cl − uptake and the diazepam potentiation of GABA-stimulated 36Cl − uptake in microsacs from cerebral cortex of both groups of animals. We found no differences in the GABA-stimulated 36Cl − uptake between adult and aged animals, and diazepam failed to potentiate GABA-induced 36Cl − flux in the aged cortical 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 transition test in the aged rats, while there was a shift to the left in the diminution of locomotor activity evaluated by the open-field test. We conclude that the pharmacodynamic changes observed in cortical GABA A receptors in aged rats could partially explain the lack of anxiolytic-like action but not the oversedation evidenced in this group of animals.