3,4-Dihydroxyphenylacetic acid (DOPAC) as an index of noradrenaline turnover: effects of Hydergine and vincamine.
Among the drugs commonly used in the treatment of memory disorders of the elderly, vincamine and hydergine have been shown to moderately increase the firing rate of noradrenergic locus coeruleus (LC) neurons. Since changes in electrical activity of noradrenergic neurons are generally reflected in corresponding alterations of the turnover of this transmitter, the effects of these drugs on the accumulation of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) in the presence and absence of the dopamine-beta-hydroxylase inhibitor, FLA 63, were studied in the LC as well as in two of its projection areas, the hippocampus and the cerebellum. Characterization of this procedure with the alpha 2-adrenoceptor antagonist, idazoxan, the corresponding agonist, clonidine, the alpha 1-adrenoceptor antagonist prazosine, and haloperidol, suggested that--DOPAC changes are more suitable than those of DA or DOPAC/DA ratios in reflecting changes in noradrenaline (NA) turnover, inhibiting DBH is advantageous if NA turnover is to be measured in projection areas, but not in LC, and haloperidol and prazosine, in principle, did not affect NA turnover. Vincamine and hydergine at 10 mg/kg doses, at which they were reported to increase LC firing by 50%, did not induce a change in NA turnover in any of the areas. This, together with the data obtained with haloperidol, suggests that a minimal increase in the firing rate of LC cells (+140%) is required before it could influence the turnover of NA, as measured by DOPAC changes. Thus, the stimulating effect of nootropics on the central noradrenergic system may be more sensitively detected by electrophysiological techniques than by biochemical ones.
Boulat
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O
Research Department, CIBA-GEIGY AG, Basel, Switzerland.
Waldmeier
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P
Maitre
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis*; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019329:Idazoxan; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D014749:Vincamine / Q000494:pharmacology*
D004146:Dioxanes; D015102:3,4-Dihydroxyphenylacetic Acid; D004088:Dihydroergotoxine; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D014749:Vincamine; D004299:Dopamine beta-Hydroxylase; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan