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U Strömbom

Publications and source records attributed to U Strömbom.

28 records · Page 2Linked to original sources
PubMed1977

Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine.

Administration of 0.025--0.1 mg/kg of apomorphine i.p. to mice produced a dose-dependent locomotor depression. Haloperidol, 0.025 mg/kg, produced locomotor stimulation, whereas 0.1 mg/kg caused locomotor depression. Pretreatment with haloperidol also reversed the depression caused by apomorphine. The functional antagonism is discussed in terms of a possible agonist-antagonist interaction on dopaminergic autoreceptors.

Animals↗
PubMed1976

Catecholamine receptor agonists: effects on motor activity and rate of tyrosine hydroxylation in mouse brain.

Motor activity during the first 5 min in a motility meter was measured in mice given 0.025-3.2 mg/kg of the dopamine and noradrenaline receptor agonists apomorphine and clonidine, respectively. The accumulation of Dopa, as induced by the inhibitor of aromatic amino acid decarboxylase, NSD 1015, was measured in parallel in two dopamine-rich regions, i.e. the limbic system and the corpus striatum, and in two noradrenaline-rich regions, i.e. the neocortex and the lower brain stem. Low doses (0.025-0.2 mg/kg) of apomorphine reduced locomotion in a dose-dependent manner, while the reduction after higher doses was less pronounced, indicating a biphasic dose-response relationship. Clonidine caused a dose-dependent locomotor depression. When low doses of the two drugs were combined, the inhibitory effect observed was at least additive. When clonidine was combined with a high dose of apomorphine (0.8 mg/kg), it caused a significant inhibition of locomotion in a dose of 0.1-0.2 mg/kg, but not after 0.8 mg/kg, indicating a biphasic dose-response relationship. Either drug given alone reduced Dopa accumulation after inhibition of its decarboxylation, in all regions, but smaller doses of apomorphine had a clearcut effect only in the dopamine-rich regions, whereas the lowest dose of clonidine investigated (0.05 mg/kg) had an inhibitory effect on Dopa formation only in the neocortex. The relationship between the dose of apomorphine and Dopa formation in the neocortex appeared biphasic, the highest dose (3.2 mg/kg) having no significant effect. Further, apomorphine in this dose accelerated the disappearance of noradrenaline after inhibition of synthesis by alpha-methyltyrosine. Reversal of reserpine-induced suppression of motor activity was taken to indicate postsynaptic receptor activation. The threshold dose of apomorphine causing reversal was 0.2 mg/kg. The inhibitory effect of e.g. 0.05 mg/kg on locomotion and on Dopa formation suggests a preferential activation of inhibitory autoregulatory dopamine receptors by low doses of this drug. A similar trend was observed for clonidine. The basal importance of dopamine neurones for the locomotor function studied in the present paper is illustrated by the marked inhibition by low doses of apomorphine. On the other hand, the observations with clonidine suggest a somewhat less striking and perhaps less direct influence of noradrenaline neurones on motor activity. Mice with a low motor activity, as induced e.g. by reserpine or, in another experiment, mice adapted to the motility meter, displayed an increased motor activity after higher doses of apomorphine (from 0.2 and 2 mg/kg, respectively), whereas all doses depressed the initial high motor activity. Probably, high motor activity requires active dopamine neurones, making this behaviour more susceptible to interference with autoregulatory mechanisms, whereas a low basal activity may be more affected by activation of postsynaptic dopamine receptors.

Animals↗
PubMed1976

Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents.

The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.

Adrenergic alpha-Antagonists↗
PubMed1975

Effects of low doses of catecholamine receptor agonists on exploration in mice.

Female mice were given 0.025--0.8 mg/kg of the dopamine and noradrenaline receptor agonists apomorphine and clonidine, respectively, and the effect on explorative behaviour of these drugs was tested in a Y-shaped runway for three minutes. Saline-treated controls displayed a stable exploratory behaviour, declining during the time period measured. The decline probably reflects adaptation to the new environment. Apomorphine depressed the activity, but the configuration of the time curve was the same as in controls. Clonidine also depressed the exploratory activity and further appeared to break the pattern of adaptation, the activity in clonidine-treated mice being low from the beginning. The higher doses of the drugs, alone or in combination, caused a pronounced suppression of the exploration. These mice were observed for ten minutes, under which period their exploration of the runway was not increased, as compared with the first three minutes. The smaller doses used are not known to cause functionally measureable activation of postsynaptic catecholamine receptors. On the other hand these doses are known as cause inhibition of firing in the respective presynaptic neurons and also inhibition of synthesis of the respective transmitter. Thus the present findings are interpreted to be due to presynaptic inhibition of the respective neurons. Clonidine caused a more pronounced inhibition of the exploration than apomorphine, suggesting nordrenaline to be of particular importance for exploratory behaviour.

Animals↗