Age-Related Decrements in the Muscarinic Enhancement of K(+)-Evoked Release of Endogenous Striatal Dopamine: An Indicator of Altered Cholinergic-Dopaminergic Reciprocal Inhibitory Control in Senescence

摘要

Previous experiments have indicated that the release of striatal dopamine (DA) is controlled by inhibitory DA autoreceptors which are mediated by inhibitory cholinergic heteroreceptors (HTRs). Activation of the HTRs by muscarinic or nicotinic agonists potentiates the potassium cation -evoked release of DA from the striatum. Present experiments were carried out to determine if this relationship is altered as a function of aging. Cross-cut striatal tissue slices obtained from 3 age-groups (6,12-18 and 24 months) Wistar rats were superfused with a modified Krebs-Ringer basal release medium containing 2.5 mM potassium chloride. The medium was switched to one containing 30 mM KCI and depending upon the experiment, 1 of 4 concentrations of a particular muscarinic (oxotremorine, pilocarpine, carbachol or bethanecol) or nicotinic (nicotine) agonist. Results indicated that the efficacy of the muscarinic agonists was reduced in an age-dependent manner with the oldest age groups showing the smallest enhancement. The age at which the decline was seen was dependent on the muscarinic agonist that was applied. Results are discussed in terms of specific deficits in the muscarinic control of striatal DA autoreceptors in senescence. These decrements occur as a result of age-related alterations in the conformation/orientational state of the muscarinic receptors regulating striatal DA release. Reprints. (AW)