1,721,339 research outputs found

    Neonatal hypothyroidism induces striatal dopaminergic dysfunction

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    Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied

    Dopaminergic deficit and mood disorders

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    The roles of serotonin and noradrenaline in the pathogenesis of mood disorders have been elucidated by numerous studies, which support the therapeutic use of tricyclic antidepressants and selective serotonin re-uptake inhibitors. The same has not occurred for dopamine, notwithstanding the fact that the crucial role of the mesolimbic dopaminergic system in behaviour has been known to researchers for many years. The objective of this article is to provide an overview of the animal data that demonstrate the importance of dopamine in animal behaviour and suggest that dopaminergic deficiency may cause a number of psychiatric symptoms in man. © 2002 Lippincott Williams & Wilkins

    Evolution of the dopaminergic system and its relationships with the psychopathology of pleasure

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    This paper summarizes the fundamental steps in the evolution of the dopaminergic system. A rudimentary dopaminergic system is present in primitive creatures, already able to select information processing, modulate 'emotional' behaviours and react to perturbations in environmental conditions. Pharmacological manipulations of the dopaminergic transmission are able to modify basic behaviours present in all animals from fishes to lizards to mammals. The ability to put the organism in motion and the hedonic capacity of giving pleasure, would justify the conservation through evolution of such a neuronal system. The fact however that the dopaminergic system has remained identical for the last several centuries, while many external conditions which interfere with its physiology have dramatically changed, may contribute to explain the transition from the original vital advantages of the dopaminergic system to its crucial role in the psychopathology of pleasure
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