Interactions between the noradrenergic and dopaminergic neurotransmitter systems in the rat brain

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dc.contributor.advisorTaljaard, J. J. F.en_ZA
dc.contributor.advisorRussel, V. A.en_ZA
dc.contributor.authorAllin, Rosemaryen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Department of Pathology.
dc.date.accessioned2012-08-27T12:26:47Z
dc.date.available2012-08-27T12:26:47Z
dc.date.issued1990
dc.descriptionUniversiteit van stellenbosch dissertations medicine.
dc.description.abstractENGLISH ABSTRACT: The development of a dissection technique enabled the nucleus accumbens to be dissected into six and the striatum into eighteen discrete areas. The concentration of monoamines in these areas was analysed by high performance liquid chromatography (HPLCl with electrochemical detection. The distribution of the different monoamines in the nucleus accumbens was not identical. In general, concentrations were found to be low in the rostral area of the nucleus accumbens. Marked differences were observed in the medial area. Dopamine (DA) levels were significantly lower in the ventrorostral than in the dorsorostral nucleus accumbens and high in both medial and caudal areas. Noradrenaline (NA) and serotonin (5-HT) levels were considerably lower than those of DA. The NA concentration was highest in the caudal area of the nucleus accumbens and the 5-HT concentration was highest in the ventrocaudal area There was evidence for a rostrocaudal decrease in DA and 5-UT turnover in the nucleus accumbens. In the striatum, DA levels were higher rostrally than caudally, the lowest levels being found in the globus pallidus. NA levels were low throughout the striatum but significantly higher in the globus pallidus 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels were higher ventrally than dorsally and ancreased along the rostrocaudal axis. Selective lesioning of the locus coeruleus (LC) noradrenergic neurons by the administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) or by direct infusion of 6-hydroxydopamine (6-OHDA) resulted in a decrease in NA concentration in the rostral area or the nucleus accumbens. DA and 5-HT levels were not affected by those lesions. DSP4 lesions caused increased 3,4-dihydroxyphenyl acetic (DOPAC) turnover in the ventromedial and ventrocaudal areas, indicating increased catechol-O-methyitransferase (COMT) activity in these areas, 6-OHDA lesions of the medial forebrain bundle (MFB) resulted in decreased NA and DA levels in all areas of the nucleus accumbens. DA turnover was increased, indicating increased monoamine oxidase (MAO) activity in the medial and caudal areas after MFB lesions. lncreased 5-HIAA/5-HT ratios were also found in the medial and caudal areas. The distribution or DA DI and D2 receptors in the nucleus accumbens was determined by means of radioligand binding assays [3H|SCH23390 was used to label DA D1 receptors and [3H]spiperone was used for DA D2 receptors. The distribution of DA D1 and D2 receptors was not superimposable although there was considerable overlap. DA D1 receptor density roughly followed the DA innervation, being low rostrally and high medially and caudally. There were no dorsoventral differences. In the ventrorostral area it appears that relatively few, more active neurons can activate a similar number or postsynaptic DA D1 receptors. DA D2 receptor density was lowest in the ventrorostral area, highest in the dorsomedial area and similar in the remaining areas of the nucleus accumbens. Chronic treatment with desipramine resulted in no significant changes in DA D1 or D2 receptor number or affinity in the nucleus accumbens, therefore increased dopaminergic transmission occurring after chronic antidepressant treatment would appear not to be due to direct changes in DA receptor binding.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: 'n Disseksietegniek is ontwikkel waardeur die nucleus accumbens in ses en die striatum in agtien diskrete areas gedissekteer kon word. Monoamienkonsentrasies in hierdie areas is deur middel van hoë werkverrigtings-vloeistofchromatografie met elektrochemiese deteksie geanaliseer. Die verspreiding van die verskillende monoamienes in die nucleus accumbens was oneweredig. Oor die algemeen is 'n lae monoamienkonsentrasie in die rostrale gedeelte waargeneem. Duidelike verskille is in die mediale gedeeltes gemeet. Dopamien(DA)- vlakke was betekenisvol lae in die ventrorostrale area van die nucleus accumbens as in die dorsorostrale area, terwyl hoër vlakke in beide die mediale en kaudale areas waargeneem is. Die vlakke van norsaronalien (NA) en serotonien (5-HT) was heelwat laer as die vlakke van DA. Die NA-konsentrasie was die hoogste in die kaudale area van die nucleus accumbens en die 5-HT-vlakke die hoogste in die ventrokaudale area. Dit wil voorkom asof die omset van beide DA and 5-HT in die rostrale gedeelte van die nucleus accumbens laer is as in die kaudale gedeelte. In die striatum is gevind dat DA-vlakke rostraal hoër is as kaudaal met die laagste vlakke in die globus pallidus NA-vlakke was laag in die striatum maar betekenisvol hoër in die globus pallidus. 5-HT en 5-hidroksieindonlasynsuur(5-HIAA)-vlakke was hoër in die ventrale dele as in die dorsale dele en is verhoog langs die rostrokaudale as. Selektiewe beletseling van die locus coeruleus (LC) noradrenerge neurone deur toediennig van N-(2-chloroethiel)-N-etiel-2- bromobenzylamien hidrochloried (DSP4) of deur direkte inspuiting van 6-hidroksiedopamien (6-OHDA), het 'n verlaging in die NA-konsentrasie van die rostrale nucleus accumbens area veroorsaak. DA- en 5-HT-vlakke is nie deur hierdie beletseling beïnvloed nie. DSP4-beletseling het 'n verhoging in die 3,4-dihidroksie-fenielasynsuur (DOPAC)-omset in die ventromediale en ventrokaudale areas veroorsaak wat dui op 'n verhoogde katesjol-0-metiel-transferase (COMT) aktiwiteit in hierdie areas. 6-OHDA beletsing van die mediale voorbreinbondel (MVB) het 'n verlaging in die vlakke van NA en DA in al die areas van die nucleus accumbens veroorsaak. Die DA-omset was verhoog en dui op 'n verhoging in die aktiwiteit van monoamien-oksidase (MAO) in die mediale en kaudale areas na die beletseling van die MVB. Ook is 'n vehoging in die 5-HIAA/5-HT verhouding in die mediale en kaudile areas waargeneem. Die verspreiding van DA D1- en D2-reseptore in die nucleus accumbens is bepaal deur middel van radioligand-bindingsmetodes. [3H]SCH23390 is gebruik om die DA D1-reseptor te merk en [3H]spiperoon om die DA D2-reseptor te merk. Die verspreiding van DA D1- en D2-reseptore was nie identies nie alhoewel daar 'n groot mate van oorvleueling was. Die DA D1-reseptordigiheid het rofweg ooreengekom met DA innervering en was dus laag rostraal en hoog mediaal en kaudaal. Daar was geen dorsoventrale verskille nie. Dit wou voorkom asof relatief minder, maar meer aktiewe neurone in die ventrorostale gedeelte voorkom wat 'n ooreenkomstige aantal postsinaptiese DA D1-reseptore kan aktiveer. DA D2-reseptordigtheid was die laagste in die ventrorostrale gedeelte en die hoogste in die dorsomediale area van die nucleus accumbens, maar het nie in die oorblywende areas verskil nie. Kroniese behandeling van rotte met desipramien het geen veranderings in die DA D1- en D2-reseptorgetal of affiniteit in die nucleus accumbens tot gevolg gehad nie. Dit wil dus voorkom asof die verhoging in dopaminerge transmissie na kroniese behandeling met antidepressiewe middels nie die direkte gevolg van 'n verandering in DA reseptorbinding is nie.af_ZA
dc.format.extent244 pages
dc.identifier.urihttp://hdl.handle.net/10019.1/68844
dc.language.isoen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.rights.holderStellenbosch University
dc.subjectNeurotransmitter receptorsen_ZA
dc.subjectDissertations -- Medicineen_ZA
dc.subjectUCTDen_ZA
dc.titleInteractions between the noradrenergic and dopaminergic neurotransmitter systems in the rat brainen_ZA
dc.typeThesis
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