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.
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 nicotine agonists potentiates the K+-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 KCl. After a 30-min equilibration period, a 5-min baseline fraction was collected from each chamber. The medium was then switched to one containing 30 mM KCl, and depending upon the experiment, 1 of 4 concentrations of a particular muscarinic (oxotremorine, pilocarpine, carbachol or bethanecol) or nicotinic (nicotine) agonist. In some experiments DA autoreceptor function was assessed directly with haloperidol. Six 5-min fractions were taken during depolarization. DA release was assessed using high performance liquid chromatography coupled to electrochemical detection. 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. Deficits were seen as early as 12 months when full agonists (e.g. carbachol) were applied, but did not appear until 18 months when partial agonists (e.g. oxotremorine) were applied. These age-related alterations were not seen when haloperidol or nicotine were used to enhance the K+-evoked release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging / Q000378:metabolism*; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D001626:Bethanechol Compounds; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010095:Oxotremorine; D011189:Potassium Chloride; D009538:Nicotine; D002217:Carbachol; D006220:Haloperidol; D004298:Dopamine