Details

Autor(en) / Beteiligte

• Vivas Sabido, Nuria Maria

Titel

Action of tacrine in relation to adrenergic neurotransmission: Correlations with cognitive dysfunction in rats

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1993

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The pharmacological approaches for the treatment of the cognitive dysfunctions of normal and pathological ageing have been based on the facilitation of cholinergic transmission, without consistent results. An exception is tacrine, primarily used for its properties as an anticholinesterase which has been demonstrated to be effective in Alzheimer's disease. The pharmacology of this compound is complex and its efficacy may depend on different neurochemical parameters. A relationship between the cholinergic and adrenergic neurotransmitter systems has been proposed to have a role in learning and memory. Therefore, the aim of the present work has been to analyze the possible participation of central $\beta$ adrenergic systems in the action of tacrine on age-associated memory impairment, using functional and neurochemical approaches. The results suggest that the ability of tacrine to reduce the cognitive deficits observed in middle-aged rats is related to an alteration in the $\beta$ adrenoceptor-coupled signal transduction system in the cerebral cortex and hippocampus. This neurochemical action turned out to be specific for tacrine and may reinforce physiological aspects of memory consolidation. The in vitro characterization of the mechanism of action leads to the suggestion that tacrine does not act on the $\beta$ adrenoceptor, since it induces a progressive decline in the ability of isoprenaline to stimulate cyclic AMP production. Neither does tacrine act on the catalytic subunit of the enzyme, but its action may depend on modifications of the cyclic AMP metabolic processes, in conditions where they are altered, as occurs with ageing. Finally, the cholinergic system plays a permissive role in the action of tacrine, and its activation may be necessary but may not be sufficient to reproduce its effects on cognition, thereby reinforcing the notion of a relationship between the cholinergic and adrenergic systems in the brain. Finally, the experiments show that tacrine does not exert actions on $\alpha\sb1$-adrenoceptor coupled signal transduction systems. The present results suggest that the effectiveness of tacrine may depend on its action on the $\beta$ adrenoceptor-coupled signal transduction system. This may constitute the basis of its effectiveness in improving the age-associated deterioration, because of its ability to modify noradrenergic and cholinergic systems.