Boer, Peter de

English

ARTS repository - University of Groningen

   University of GroningenDopamine-acetylcholine interactions in the rat striatum in vivo microdialysis studiesBoer, Peter deIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1992Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Boer, P. D. (1992). Dopamine-acetylcholine interactions in the rat striatum in vivo microdialysis studies. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 21-06-2022SUMMARYThe observation that both anticholinergics and dopamine agonists ameliorateparkinsonian s;,.rnptoms has generated a great number of neurochemical studiesaimed to establish an interaction between these two transmitter systems. Fromthese studies it was concluded that dopamine inhibits the output of acetylcholinein the striatum via a dopamine D2 receptor. Furthermore, the increases in theoutput ofacetylcholine or the decreases in the tissue content ofacetylcholine aftersystemic administration of dopamine receptor blockers indicated that dopaminetonically inhibited striatal cholinergic neurons. Before the development of a brainmicrodialysis method for the measurement of acetylcholine, the studies on thedopamine-acetylcholine interactions in the striatum were done using in vitrorelease studies, tissue measurements or using push-pull cannulas in gallamineimmobilized cats. Since brain microdialysis provides a unique opportunity tomeasure neurochemical events in freely moving, conscious animals, the striataldopamine-acetylcholine interactions were investigated using this method.Initially we failed to show an interaction between nigrostriatal dopaminergicfibers and cholinergic interneurons using brain microdialysis. Since these Íindingswere largely at variance with the prevailing view in the scientific community, wedecided to study some methodological aspects pertaining to microdialysis studiesto validate the method and to provide further evidence that would either confirmor deny the existence of a striatal dopamine-aceQrlcholine interaction.In the introduction the role of acelrlcholine and dopamine in basal gangliafunctioning is discussed. Both dopamine and acetylcholine are thought to beimportant in the gating of information that is largely derived from the cortexflowing through the striatal cell mosaic to the basal ganglia output centers.Furthermore, the possibility that dopamine and acetylcholine interactions occur viaa common target neuron is discussed in the light of electrophysiological andanatomical evidence. It is concluded that there might be a convergence ofcholinergic and dopaminergic input on the GABA-ergic medium spiny neuron, butr42thtriinlItaclreÍa lac(mtDêfollcoraceperchounlconmmrec(agocalcthemulmmcou.dec3.4atr<onists ameliorateochemical studieser systems. Fromrt of aceflcholiner increases in theLcetylcholine afterrd that dopaminerpment of a brainte studies on there using in vitrorlas in gallaminee opportunifir tonals, the striatals method.fal dopaminergic.ce these findingsc community, weodialysis studiestd either confirmction.in basal ganglia: thought to befrom the cortexoutput centers.lctions occur viaLysiological andconvergence ofiny neuron, butthat electrophysiological data not clearly show an antagonistic interaction of thetransmitters dopamine and acetylcholine.In chapter I we discuss the effect of neostigmine (a acet5rlcholinesteraseinhibitor), coinfused in our artiÍicial CSF, on muscarinic autoreceptor responses.It is shown that 0.1 ptmoVl neostigmine increases the extracellular levels ofacetylcholine about ten-fold and that the increase in extracellular acet;rlcholineresults in the attenuation of the effect of the muscarinic agonist oxotremorine anda potentiation of the effect of the muscarinic antagonist atropine.In chapter 2 the muscarinic autoreceptor that modulates the output ofacetylcholine from the striatum is further characterized by infusing the selectivemuscarinic antagonists 4-DAMP, AF-DX 116 and pirenzepine. It is shown that 4-DAMP increases the output of acetSzlcholine from the striatum most potently,followed by pirenzepine and AF-DX 116 respectively. From these observations weconclude that an Mr-muscarinic autoreceptor modulates the overflow oface[rlcholine from the striatum.In chapter 3 the effect of the calcium concentration of the microdialysisperfusion fluid is tested both on autoreceptor and heteroreceptor responses ofcholinergic and dopaminergic neurons. Whereas the output of acetylcholine wasunresponsive to D2 receptor activation at elevated perfusion fluid calciumconcentrations (3.4 mmol/l), at more physiological calcium concentrations (1.2mmoVl) an inhibition of the output of acetylcholine could be measured after D2receptor stimulation. It is shown that the attenuation of the effect of dopamineagonists can be attributed to muscarinic autoreceptor occupation at 3.4 mmol/lcalcium. Infusion of the dopamine receptor antagonist (-)-sulpiride did not affectthe output of acetylcholine either at 1.2 mmoVl or 3.4 mmol/l calcium. Themuscarinie agonist oxotremorine also decreased the output of acetylcholine at 1.2mmoVl calcium but not at 3.4 mmoVl calcium. The output of striatal dopaminecould be increased after infusion of the dopamine antagonist (-)-sulpiride anddecreased after infusion of the dopamine agonist (-)-N-0437 both at 1.2 mmoVl and3.4 mmoVl calcium present in the perfusion fluid. Neither oxotremorine, noratropine could affect the output of striatal dopamine at both calcium143concentrations. The percentual increase in the output of dopamine after infusionof the dopamine releasing drug (+)-amphetamine or the dopamine uptake inhibitornomifensine was greater at 1.2 mmol/l than at 3.4 mmol/l calcium.These studies indicate that the output of acetylcholine is modulated by muscarinicautoreceptors and dopaminergic (D2) heteroreceptors. The D2 receptors areprobably not tonically activated. The output of striatal dopamine is modulated bydopamine (D2) autoreceptors but not by muscarinic heteroreceptors.Whereas in chapter 3 the drugs were infused into the striatum, in chapter 4the results of systemic applications of dopamine agonists and antagonists arestudied on the release of acegrlcholine. The dopamine agonists apomorphine andN-0437 decrease the output of striatal acetylcholine, whereas the dopamineantagonists sulpiride and haloperidol increase the output ofstriatal acetylcholine.In chapter 5 the effects of dopamine D1 and D2 receptor ligands, thedopamine releaser (+)-amphetamine and the dopamine uptake inhibitornomifensine are studied on the release of striatal acetylcholine as a function of thepost-implantation interval of a microdialysis probe. It is shown that striataldopamine D2 but not Dl receptors are involved in the modulation of striatalacef'lcholine release. The dopamine D2 receptors are not occupied 16-24 h aÍterprobe implantation, but a tonic interaction between dopaminergic and cholinergicsystems can be seen 40-48 h after probe implantation. The dopamine releasingdrug (+)-amphetamine and the dopamine uptake inhibitor nomifensine dose-dependently increase the output of striatal dopamine. However, only when theextracellular dopamine levels are more than sevenfold increased, the output ofstriatal acetylcholine is affected. These studies confirm the existence of a dopamineD2 receptor mediated inhibition of the release of acetylcholine and the existenceof a tonic inhibition of the cholinergic interneuron in the striatum by dopamine.Furthermore, the importance of the post-implantation of a microdialysis probe forthe pharmacological responsiveness of striatal cholinergic neurons is shown.The theme of chapter 6 might be clinically relevant. Patients with Parkinson'sdisease are currently treated with L-DOPA, an ergot drug of a combination of thesedrugs. The neurochemical effect of the ergot drugs and L-DOPA on the release oft441€CSbSrSiGmlth,mine after infusionne uptake inhibitor:ium.ated by muscarinicD2 receptors arene is modulated byrptors.tum, in chapter 4Ld antagonists areapomorphine andns the dopamine.atal acetylcholine.rptor ligands, theuptake inhibitors a function of theown that striatalrlation of striatalried 16-24 h afteric and cholinergicpamine releasing.omifensine dose-r, only when theed, the output ofrce of a dopaminemd the existencerm by dopamine.lialysis probe forrs is shown.vith Parkinson'sbination ofthesern the release ofstriatal acetylcholine was assumed to be similar. However, in this study we showthat the output of acetylcholine from the striatum is increased after systemicapplication of L-DOPA. In contrast, the output of striatal acetylcholine decreasesafter systemic injections of bromocriptine. These effects are not only seen inanimals with an intact nigrostriatal dopaminergic system, but also in animalstreated with the dopaminergic neurotoxin 6-hydroxydopamine. It is speculated thatthe increased output of striatal acetylcholine is the result of the stimulation ofextrastriatal dopamine Dl receptors. This topic is further discussed in thediscussion.Not only dopaminergic systems modulate the output of acetSrlcholine from thestriatum. In chapter 7 we show that in addition GABA-ergic receptor activationby direct acting receptor ligands modulates the output of striatal acet;rlcholine.Striatal acetylcholine release may be tonically inhibited via a GABAo-receptor.Since intrastriatal infusion of dopamine Dl agonists that increase the output ofGABA does not affect the output of acetylcholine, we conclude that the GABA-ergicmodulation of striatal cholinergic neurons occurs via GABA-ergic cell elements inthe striatum that have no D1 receptors.t45it ,

Dopamine-acetylcholine interactions in the rat striatum in vivo microdialysis studies

https://pure.rug.nl/ws/files/14486178/Boer.pdf

Dopamine-acetylcholine interactions in the rat striatum in vivo microdialysis studies

Abstract

Similar works

Full text

Available Versions

ARTS repository - University of Groningen