Evidence for a dopaminergic dominance in the 4,α-dimethyl-m-tyramine-induced hypermotility in mice
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The effects of various drugs on the hypermotility induced in mice by 4,α-dimethyl-m-tyramine (H 77/77) was investigated.
The H 77/77-induced hypermotility was strongly inhibited by centrally acting dopamine-(DA-) receptor blockers (e.g., benperidol, fluspirilene, haloperidol) and potentiated by drugs increasing central DA activity by release of DA, by uptake inhibition (d- and l-amphetamine, nomifensine), or by inhibition of monoamine oxidase (e.g., parglyline, chlorgyline). While DA-receptor agonists (e.g., bromocriptine, ergocornine) potentiated hypermotility, the effects of those having a short duration of action (apomorphine, piribedil) were partly obscured. The catecholamine precursor L-dopa increased hypermotility only slightly, but its effect was markedly potentiated after inhibition of dopa decarboxylase.
Inhibition of tyrosine hydroxylase with α-methyltyrosine methyl ester HCl (H 44/68) totally blocked H 77/77 hypermotility. Inhibition of noradrenaline (NA) synthesis with bis-(4-methyl-l-homopiperazinyl thiocarbonyl)-disulphide (FLA 63) had no significant effect, whereas after sodium diethyldithiocarbamate (DDC) there was a moderate decrease in motility of about 25%.
Blockers of α- and β-adrenoceptors either did not affect H 77/77 hypermotility (e.g., WB 4101, pindolol) or inhibited it only at very high doses (e.g., phentolamine, propranolol). α-Adrenoceptor agonists (clonidine, guanfacine) had no clear effects.
No correlation was found between the H 77/77-inhibiting effect of antidepressant drugs and their ability to inhibit NA uptake.
Several antiserotoninergic compounds (pizotifen, 27-096, 29-245) blocked the effects of H 77/77, and a 65% drop in hypermotility was obtained after inhibition of 5-HT-synthesis with 6-flourotryptophan. Substances that increase central serotoninergic activity (l-5-HTP, fenfluramine), however, were inactive.
Anticholinergic drugs (e.g., atropine, dexetimide) increased H 77/77 hypermotility, whereas cholinergic drugs (e.g., arecoline, physostigmine) produced no dose-related effect.
It is cocluded that DA plays a dominant role in the H 77/77-induced hypermotility in mice, although functional NA and 5-HT systems appear to be a prerequisite for the full H 77/77 effect.
Key wordsH 77/77 Dopamine Noradrenaline Serotonin Antischizophrenic drugs Antidepressant drugs
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