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

[摘要] ENGLISH ABSTRACT: The development of a dissection technique enabled the nucleus accumbens to be dissected intosix and the striatum into eighteen discrete areas. The concentration of monoamines in theseareas was analysed by high performance liquid chromatography (HPLCl with electrochemicaldetection.The distribution of the different monoamines in the nucleus accumbens was not identical. Ingeneral, 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 significantlylower in the ventrorostral than in the dorsorostral nucleus accumbens and high in both medialand caudal areas. Noradrenaline (NA) and serotonin (5-HT) levels were considerably lowerthan those of DA. The NA concentration was highest in the caudal area of the nucleusaccumbens and the 5-HT concentration was highest in the ventrocaudal area There wasevidence for a rostrocaudal decrease in DA and 5-UT turnover in the nucleus accumbens. Inthe striatum, DA levels were higher rostrally than caudally, the lowest levels being found inthe globus pallidus. NA levels were low throughout the striatum but significantly higher in theglobus pallidus 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels were higher ventrallythan 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 of6-hydroxydopamine (6-OHDA) resulted in a decrease in NA concentration in the rostral area orthe nucleus accumbens. DA and 5-HT levels were not affected by those lesions. DSP4 lesionscaused increased 3,4-dihydroxyphenyl acetic (DOPAC) turnover in the ventromedial andventrocaudal areas, indicating increased catechol-O-methyitransferase (COMT) activity inthese 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, indicatingincreased 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 bymeans 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 notsuperimposable although there was considerable overlap. DA D1 receptor density roughlyfollowed the DA innervation, being low rostrally and high medially and caudally. There wereno dorsoventral differences. In the ventrorostral area it appears that relatively few, moreactive neurons can activate a similar number or postsynaptic DA D1 receptors. DA D2 receptordensity was lowest in the ventrorostral area, highest in the dorsomedial area and similar in theremaining areas of the nucleus accumbens.Chronic treatment with desipramine resulted in no significant changes in DA D1 or D2receptor number or affinity in the nucleus accumbens, therefore increased dopaminergictransmission occurring after chronic antidepressant treatment would appear not to be due todirect changes in DA receptor binding.

[发布机构] Stellenbosch University