AGING DECREASES THE SENSITIVITY OF THE GABA CARRIER TO PROPOFOL AND ETOMIDATE

The influence of aging on the pharmacodynamics of anaesthetic agents i n the central nervous system remains poorly understood. As alpha-amino butyric acid (GABA)-mediated neurotransmission appears to be an import ant target for anaesthetics in the brain, we hypothesized that aging c ould alter the sensitivity of the GABA carrier to anaesthetics. We hav e examined the effects of etomidate and propofol on the uptake of [H-3 ]-GABA (5 min, 37 degrees C) into striatal synaptosomes of rats aged 2 , 18 and 24 months. in 2-month-old rats, [H-3]-GABA uptake was inhibit ed by nipecotic acid, a competitive inhibitor of the GABA carrier (IC5 0 = 3.6 so 0.3 mu M) Etomidate and propofol markedly reduced the activ ity of the GABA carrier, with IC50 values 58 (SD 3) and 46 (SD 3) mu m ol litre(-1), respectively. Aging increased IC50 values for these anae sthetics. Nipecotic acid was unaffected. These data suggest that aging selectively alters the action of etomidate and propofol in the mammal ian CNS.