Biomedical subjects

H Hallberg

Publications and source records attributed to H Hallberg.

23 records · Page 2Linked to original sources

PubMed1981

Increased brain serotonergic and noradrenergic activity after repeated systemic administration of the beta-2 adrenoceptor agonist salbutamol, a putative antidepressant drug.

Subchronic (5 mg/kg SC, twice daily for 14 days) but not acute administration of the beta-2-adrenoceptor agonist salbutamol to rats caused a significant increase in the accumulation of 5-hydroxytryptophan in the limbic forebrain, the corpus striatum and the cerebral cortex when measured during 30 min after inhibition of L-amino acid decarboxylase by NSD 1015 (100 mg/kg IP). Simultaneously assayed tryptophan concentrations in the same brain regions were not affected. These results indicate an increase in the in vivo rate of tryptophan hydroxylation in the brain, produced by subchronic salbutamol administration. The effect of salbutamol treatment on brain catecholamine(CA) utilization was estimated by studying the disappearance of CA in the brain after inhibition of tyrosine hydroxylase by alpha-methyltyrosine methyl ester (H 44/68), 250 mg/kg IP, 3.5 h before sacrifice. Subchronically but not acutely administered salbutamol caused both a significant increase in endogenous noradrenaline (NA) levels and an increase NA utilization. Dopamine levels and turnover were, however, not altered by either acute or subchronic treatment. The activation, probably centrally elicited, of brain NA and 5-hydroxytryptamine systems by the subchronic salbutamol regimen supports the concept of beta-adrenoceptor mediated regulation of brain monoamine systems, and could contribute to the clinically reported antidepressant activity of beta-2-adrenoceptor agonists.

Albuterol↗

PubMed1981

Effects of propranolol on the locomotor stimulation induced by activation of postsynaptic catecholamine receptors.

The present study was undertaken in order to clarify the possible involvement of a central beta-adrenoceptor mediated action on the stimulation of locomotor activity by the dopamine agonist apomorphine and the noradrenergic agonist clonidine. The effect of pretreatment with various doses of d-and dl-propranolol on apomorphine- and apomorphine plus clonidine-induced locomotor stimulation in reserpinized mice was measured in photocell activity chambers. Pretreatment with dl-propranolol prolonged the duration of apomorphine-induced locomotor stimulation without affecting the maximal level of activity. A similar tendency was seen after pretreatment with the d-form of propranolol, which has a much lower beta-receptor blocking activity. The potentiation by clonidine of the apomorphine-induced locomotor stimulation in reserpinized mice was dose-dependently reduced by pretreatment with dl-propranolol whereas d-propranolol was found to be ineffective. The results indicate that central beta-receptor mechanisms might be involved in the apomorphine plus clonidine-induced locomotor stimulation of reserpinized mice.

Animals↗

PubMed1981

Central pre- and postsynaptic monoamine receptors in antidepressant therapy.

Activation of postsynaptic noradrenergic alpha 1-receptors may be involved in the mediation of psychomotor activating effects of tricyclic antidepressant (TCA) drugs. On the other hand, the pronounced sedative properties of some TCA drugs seem to be correlated with their alpha 1-receptor blocking capacity. The presynaptic alpha 2-receptors probably mediate the feed back inhibition of central NE neurons seen after administration of TCA drugs, particularly the secondary amines. Yet other antidepressants such as mianserin are potent antagonists at central alpha 2-receptors, a phenomenon which can even cause activation of brain NE neurons and form a basis for their therapeutic action. beta-Receptor activation in the brain is also suggested to participate in the therapeutic effect of several drugs, e.g. mianserin and the putative antidepressant agent salbutamol, a beta 2- receptor agonist. A reduced central beta-receptor activation may, accordingly, contribute to depressive symptoms associated with treatment with beta-adrenoceptor blocking drugs, both by their action per se as well as by secondary effects on the monoamine systems, which we recently have demonstrated. Facilitation of brain 5-HT neurotransmission seems to be achieved with several TCA drugs not only via inhibition of reuptake but also through sensitization of postsynaptic 5-HT receptors, developing during repeated treatment. In contrast the "presynaptic" 5-HT receptors do not show increased sensitivity during chronic TCA drug treatment, thus allowing for an enhanced synaptic effect of 5-HT induced by TCA drugs.

Animals↗

PubMed1980

Reduced brain monoamine synthesis by systemic treatment with terbutaline, a beta 2-receptor agonist.

The effects of acutely (5 mg/kg s.c.) or subchronically (2.5 mg/kg s.c., twice daily, 4 days) administered terbutaline, a beta 2-receptor agonist, on the in vivo rate of tryptophan and tyrosine hydroxylation in various rat brain parts were studied. The accumulation of 5-hydroxytryptophan (5-HTP) during 30 min following treatment with NSD 1015, 100 mg/kg i.p., an inhibitor of L-aromatic amino acid decarboxylase, appeared reduced in several brain parts by the terbutaline treatments, the effect being significant in the limbic forebrain and the hemispheres after subchronic administration. This treatment also reduced the simultaneously measured accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the same brain parts as well as in corpus striatum, where the effect was seen also after acutely administered terbutaline. The concentration of tryptophan in the various brain parts was not significantly affected by the terbutaline treatments and the tyrosine levels were only reduced in some brain parts (the hemispheres and the brain stem). The central effects obtained by terbutaline treatment may be mediated indirectly via peripheral inputs to e.g. the monoamine carrying neurons and/or via putative changes in cerebral blood flow.

5-Hydroxytryptophan↗

PubMed1980

alpha- and beta-adrenoreceptor-mediated control of brain noradrenaline neurons and antihypertensive therapy.

1. The central noradrenergic nucleus locus coeruleus seems to participate in arousal reactions and cardiovascular modulation. Using single cell recording techniques and biochemical assays, we have studied locus coeruleus neuronal regulation and its interaction with antihypertensive treatments. 2. Acute (5 microgram/kg intravenously) or chronic clonidine treatment (2 microgram/ml in drinking water for 2 weeks) significantly reduced locus coeruleus neuronal activity, probably via activation of alpha 2-receptors within the nucleus. Termination of the chronic regimen increased the noradrenaline cell firing rates above baseline, a finding possibly related to the withdrawal syndrome. 3. In spontaneously hypertensive rats the activation of locus coeruleus neurons by yohimbine, an alpha 2-receptor antagonist, was increased compared with that in normotensive (Wistar-Kyoto) control rats, implying an altered alpha 2-receptor-mediated control of the central noradrenaline neurons. 4. Chronic treatment with DL-propranolol (5 or 10 mg/kg daily for 1 week) but not D-propranolol or acutely given DL-propranolol significantly reduced neuronal activity in the locus coeruleus, an effect which may relate to mental and cardiovascular actions of beta-receptor-blocking drugs. 5. In contrast, chronically given salbutamol, a beta 2-receptor agonist (5 mg/kg subcutaneously for 2 weeks), increased brain noradrenaline utilization. Thus beta-receptors probably participate in the control of brain noradrenaline neurons.

Action Potentials↗