Receptor-Mediated Alterations of Central Monoaminergic Transmission in Aged Wistar Rats
The in vivo release of brain catecholamines, the efficiency of feedback mechanisms controlling central catecholaminergic transmission, and the responsiveness of brain dopamine (DA) receptors to agonists and antagonists were studied in adult and senescent rats of the Wistar strain. After inhibition of monoamine oxidase the accumulation of 3-methoxy tyramine and normetanephrine was reduced in the forebrain of senescent animals despite elevated DA and NA levels indicating impaired catecholamine (CA) release. Consonantly, the locomotor stimulatory effect of the indirect CA agonist D-amphetamine was reduced in aged animals. However, the less pronounced hyperactivity induced by the direct DA agonists lisuride and propyl-transdihydrolisuride (propyl-TDHL) in senescent rats indicates decreased responsiveness of postsynaptic meso-limbic DA receptor as an additional causative factor. Apparently the responsiveness of postsynaptic nigrostriatal DA receptors is not altered by senescence as judged from the equal efficacy in adult and aged animals of haloperidol to cause catalepsy or of propyl-TDHL to induce stereotypies. Receptor-mediated feedback mechanisms controlling dopamine synthesis and metabolism appeared to be dampened in the senescent rats studied. The increase of dihydroxyphenylacetic acid induced by haloperidol as well as the stimulation of dopa synthesis induced by γ- butyrolactone was attenuated in senescent rats. In addition, the affinity of agonists to dopamine autoreceptors appeared to be reduced.
KeywordsLocomotor Activity Dopamine Agonist DOPAC Level Dihydroxyphenylacetic Acid Aromatic Amino Acid Decarboxylase
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