Doctoral Degrees (Chemical Pathology)

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Browsing Doctoral Degrees (Chemical Pathology) by browse.metadata.advisor "Taljaard, J. J. F."

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    Interactions between the noradrenergic and dopaminergic neurotransmitter systems in the rat brain
    (Stellenbosch : Stellenbosch University, 1990) Allin, Rosemary; Taljaard, J. J. F.; Russel, V. A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Department of Pathology.
    ENGLISH 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.