Pre-synaptic function explains age-dependent actions of general anesthetics in the rat hippocampal synaptic transmission

Mechanisms by which age modifies general anesthetic requirements remain uncertain. In order to examine the age-related modification of general anesthetics in the central nervous system, we have studied the effects of thiopental and sevoflurane on hippocampal synaptic transmission in young and elderly rats. Field potentials of area CA1 were electrically elicited in hippocampal slices from young (4-month) and elderly (2-year) male Wistat rats. The effects of sevoflurane on both excitatory and inhibitory synaptic transmission were similar in the young and elderly preparations. In contrast, thiopental produced a greater effect on inhibitory synaptic transmission in young than elderly hippocampi, whereas the actions on excitatory synaptic transmission were negligible in both preparations. Corresponding experiments revealed (a) that the duration of recurrent inhibition was more prolonged by thiopental in young compared to elderly animals and (b) that thiopental enhanced the γ-amino-butyric acid (GABA) release from pre-synaptic terminals in an age-dependent manner. The thiopental actions on GABA discharge from pre-synaptic terminals appear to be responsible for the observed difference between young and elderly animals. The age-dependent reduction in neurotransmitter stores in pre-synaptic terminals may explain the age-related alterations in general anesthetic actions.