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Biomedical subjects

A Carlsson

Publications and source records attributed to A Carlsson.

At least 361 records · Page 20Linked to original sources
PubMed1978

Antipsychotic drugs, neurotransmitters, and schizophrenia.

Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the mental and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or dopa may lead to a disturbance mimicking paranoid schizophrenia lends further support for a key role of dopamine in mental functions. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, amino acid, or peptide transmitters in schizophrenia cannot be disregarded.

Acetylcholine↗
PubMed1977

Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists.

Small doses of apomorphine (0.03-0.25 mg/kg i.p.) caused a dose-dependent suppression of the ethanol-induced (2.36 g/kg, 15% v/v, i.p.) locomotor stimulation in mice and higher doses (0.5--2 mg/kg i.p.) caused a delayed suppression. The delay increased with increased doses. Very small doses of clonidine (0.025 or 0.05 mg/kg i.p.), which per se did not or only slightly affect the activity of control mice, also markedly suppressed the ethanol-induced motor stimulation. Ethanol alone (2.36 g/kg i.p.) did not significantly affect the amount of Dopa accumulating in various mouse brain regions (limbic system, corpus striatum, hemispheres and brain stem) during 30 min following administration of 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of aromatic amino-acid decarboxylase. Both the hypothermia and the locomotor stimulation by ethanol were antagonized by NSD 1015. The reduction in Dopa accumulation induced by a small dose of apomorphine (0.25 mg/kg i.p.) in the dopamine-rich regions in the mouse brain was slightly enhanced by ethanol, whereas the clonidine-induced decrease in Dopa accumulation was, if anything, reduced. In conclusion, ethanol's behavioural stimulant action in mice can be largely suppressed by apomorphine or clonidine, drugs which in the small doses used probably inhibit central catecholamine (CA) neurons.

Animals↗
PubMed1977

Neurometabolic and behavioural effects of haloperidol in relation to drug levels in serum and brain.

A method has been developed for the quantitative determination of haloperidol in brain and other tissues. Such determinations have been made after acute and chronic administration of haloperidol to Sprague-Dawley rats. Different regions of the brain including the striatum, the limbic forebrain and the cerebellum have been analyzed separately. The haloperidol effects on Dopa formation have been studied in the same tissue samples. The stimulation of prolactin secretion via blockade of hypothalamic dopaminergic mechanisms and behavioural effects of the drug have been evaluated in parallel experiments. The elimination of haloperidol from brain tissue is a multiphasic process. The fourth phase of elimination is the slowest with a half life of 4 days. No strict correlation was found between serum and brain concentrations of haloperidol. Both after acute and chronic administration there exists apparently a saturating dose above which the brain concentration of the drug increases very little. The dose seems to coincide with that beyond which little increase in Dopa formation is observed. A pharmacokinetic analysis suggests an element of saturable binding or transfer of haloperidol to brain tissue. This mechanism is not preferentially localized to areas of brain rich in dopaminergic synapses. A good correlation was found between the haloperidol concentration in the brain on the one hand and its effects on behaviour, on serum prolactin values and on Dopa formation on the other.

Animals↗
PubMed1977

Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol.

Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine. In the rest of the hemispheres the apomorphine-induced decrease in dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol. The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine. Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect. In general, the tyrosine concentration tended to be higher on the lesioned than on the intact side in all brain structures investigated. The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow.

Animals↗
PubMed1977

The effect of intracerebroventricularly administered GABA on brain monoamine metabolism.

Intracerebroventricular injection of gamma-aminobutyric acid (GABA) was performed in male rats and the brain monoamines, 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan levels were measured. GABA induced within 30 min a marked dose-dependent increase in the brain contents of dopamine (DA), serotonin (5-HT), tyrosine and tryptophan, while noradrenaline (NA) was lowered. Large doses of GABA, i.e. 1.5-3 mg/rat, were required for these effects. Aminooxyacetic acid (AOAA), an inhibitor of GABA-transaminase, when given alone in a dose of 25 mg/kg i.p. caused a significant rise of DA, 5-HT and tryptophan. The combination of GABA and AOAA raised these levels more than either agent alone. Picrotoxin (4 mg/kg, i.p.) a claimed GABA receptor antagonist partially counteracted the GABA-induced DA rise. Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-amino-acid decarboxylase, given i.p. 5 min after GABA. GABA caused a marked rise in dopa formation both in DA- and NA-predominated brain regions. Also 5-HTP formation was enhanced. The effects on both dopa and 5-HTP formation showed marked regional differences. The data suggest that GABA, by activating specific receptors, causes inhibition of firing of dopaminergic neurones and the opposite effect on the noradrenergic neurones. The nature of the effect on 5-HT metabolism needs further investigation.

Aminobutyrates↗
PubMed1977

The effect of intraperitoneally administered GABA on brain monoamine metabolism.

GABA was injected intraperitoneally to rats in single doses of 2.5 to 1500 mg/kg. Thirty minutes after injection a dose-dependent increase in dopamine (DA) and a decrease in noradrenaline (NA) content were observed in the brain. However, in the lowest dose range these levels showed small but significant changes in the opposite direction. The accumulation of dopa after inhibition of the aromatic L-aminoacid decarboxylase was enhanced by i.p. GABA both in DA- and in NA-predominated brain regions, the dose-response relations being complex. Increased levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan as well as enhanced accumulation of 5-hydroxytryptophan, induced by decarboxylase inhibition were also observed. The general pattern of effects was similar to that previously observed after intracerebroventricular injection of GABA, although the intraperitoneal doses required were higher. It is suggested that a certain penetration of GABA from the blood into the brain can occur, leading to changes in the physiological activity of monoaminergic neurons.

Aminobutyrates↗
PubMed1977

Agonist--antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation.

The effect of haloperidol and apomorphine, and both drugs in combination, on the first steps in the synthesis of catecholamines and 5-hydroxytryptamine (5-HT) has been studied in three rat brain regions. The rate of formation of dopa and 5-hydroxytryptophan (5-HTP) was studied by measuring the accumulation of these amino acids during 30 min after administration of the inhibitor of the aromatic L-amino acid decarboxylase, NSD 1015 (3-hydroxybenzylhydrazine HCl). Haloperidol caused an increase in dopa and no change in 5-HTP formation. The threshold dose was severalfold higher in the noradrenaline-predominated hemisphere portion than in the dopamine-rich striatal and limbic regions, suggesting a higher affinity of haloperidol for dopamine than for noradrenaline receptors. Apomorphine caused a decrease in dopa formation in all three brain regions studied, although the effect was much more pronounced in the regions dominated by dopamine. The threshold dose was about 30 microng/kg, i.e. an order of magnitude lower than the threshold dose for apparent postsynaptic dopaminergic receptor activation. This discrepancy is suggested to be due to preferential activation of inhibitory dopaminergic autoreceptors by low apomorphine doses. This phenomenon may also contribute to explain the complex dose-response curves of apomorphine. Low doses of apomorphine caused a decrease and high doses an increase in 5-HTP formation. These effects, like those on noradrenaline synthesis, are suggested to be secondary to activation of dopaminergic pre- and post-synaptic receptors. The interaction between apomorphine and haloperidol with respect to dopa formation appears to be largely explicable on the assumption of a competition between an agonist and an antagonist for dopaminergic receptors. However, very large doses of apomorphine cause a haloperidol-resistant inhibition of tyrosine, and probably also tryptophan, hydroxylation, which may be due to a direct inhibition of the aromatic amino acid hydroxylase involved.

5-Hydroxytryptophan↗
PubMed1977

Does dopamine play a role in schizophrenia?

Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets of these drugs for the mental and the extrapyramidal actions respectively. Dopaminergic hyperfunction, induced by amphetamines or dopa, may lead to a disturbance mimicking paranoid schizophrenia, lending further support for a key role of dopamine in mental functions. While a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, aminoacid or peptide transmitters in schizophrenia cannot be disregarded.

5-Hydroxytryptophan↗
PubMed1977

Reduced adrenal amine synthesis in spontaneously hypertensive rats after long-term treatment with propranolol.

Male spontaneously hypertensive rats were either fed a diet containing 3 mg/g of (+/-)-propranolol, giving a mean daily intake of 178 +/- 4.2 mg/kg, or a control diet from 7 weeks of age for 6 months. Three days after cessation of propranolol-treatment, the arterial blood pressure of the treated group was about 10% lower than that of the control group. Adrenal dopamine content and tyrosine hydroxylase activity were reduced to 76% and 71% of the control values, respectively. The results indicate that propranolol causes a reduced sympathetic discharge through its central action, although blockade of beta-adrenoceptor-mediated local regulatory mechanisms cannot be excluded.

Adrenal Glands↗
PubMed1977

Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain.

The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes.

5-Hydroxytryptophan↗
PubMed1977

Exposure of animals and man to toluene.

Twenty rats were exposed for 60 min to 14C-labeled toluene (1,950 mg/m3) in the inspired air. The largest amounts of toluene and its metabolites were found in the white adipose tissue. In a second series of experiments seven healthy male subjects were exposed to 375 mg/m3 of toluene in the air rest and during light, moderate and heavy physical exercise on a bicycle ergometer. The duration of each exposure period was 30 min. Of the seven male subjects three were thin, one was slightly overweight, and three were excessively overweight. The concentration of toluene in the alveolar air and the total uptake of toluene were determined during exposure. The thin subjects had a higher concentration of toluene in alveolar air than the other subjects both at rest and during exercise. The total uptake of toluene in the body during exposure showed that the subjects with the least amount of adipose tissue had the smallest uptake and the subjects with the largest amount of adipose tissue had the largest uptake.

Adipose Tissue↗