Differential changes in presynaptic modulation of transmitter release during aging.

The purpose of this study was to assess the functional role of presynaptic alpha 2-autoreceptors in noradrenergic transmission in the hippocampus and dopamine-2 heteroreceptors in cholinergic transmission in the striatum in young, adult, and senescent rats. Male and female Wistar rats (4, 12, and 24 months old) were used and the release of radioactivity from striatal and hippocampal slices that had been loaded either with [3H]choline or with [3H]norepinephrine was measured at rest and in response to field stimulation (2 Hz, 360 shocks). The release was challenged by sulpiride, a selective dopamine-2 receptor antagonist, and CH-38083, a selective alpha 2-adrenoceptor antagonist. The dissociation constant and the number of alpha 2-adrenoceptors was also determined by binding studies using [3H]yohimbine as ligand in crude membrane preparations of frontal cortex. There were an age-related changes in alpha 2-adrenoceptor-mediated negative feedback modulation of norepinephrine release and in the density and dissociation constant of alpha 2-adrenoceptors. They were reduced in senescent rats. In contrast the presynaptic modulation of striatal cholinergic transmission by dopamine-2 receptors was not altered during aging, but the storage capacity of and the release of acetylcholine from cholinergic interneurons was significantly lower.