DIFFERENTIAL CHANGES IN PRESYNAPTIC MODULATION OF TRANSMITTER RELEASEDURING AGING

The purpose of this study was to assess the functional role of presyna ptic alpha(2)-autoreceptors in noradrenergic transmission in the hippo campus and dopamine-2 heteroreceptors in cholinergic transmission in t he striatum in young, adult, and senescent rats. Male and female Wista r rats (4, 12, and 24 months old) were used and the release of radioac tivity from striatal and hippocampal slices that had been loaded eithe r with [H-3]choline or with [H-3]norepinephrine was measured at rest a nd in response to field stimulation (2 Hz, 360 shocks). The release wa s challenged by sulpiride, a selective dopamine-2 receptor antagonist, and CH-38083, a selective alpha(2)-adrenoceptor antagonist. The disso ciation constant and the number of alpha(2)-adrenoceptors was also det ermined by binding studies using [H-3]yohimbine as ligand in crude mem brane preparations of frontal cortex. There were an age-related change s in alpha(2)-adrenoteptor-mediated negative feedback modulation of no repinephrine release and in the density and dissociation constant of a lpha(2)-adrenoceptors. They were reduced in senescent rats. In contras t the presynaptic modulation of striatal cholinergic transmission by d opamine-2 receptors was not altered during aging, but the storage capa city of and the release of acetylcholine from cholinergic interneurons was significantly lower.