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A Carlsson

Publications and source records attributed to A Carlsson.

At least 217 records · Page 12Linked to original sources
PubMed1987

Region-selective activation of brain monoamine synthesis by sexual activity in the male rat.

In vivo catecholamine and 5-HT synthesis during sexual activity and treadmill locomotion was estimated in male rats by measuring the accumulation of DOPA and 5-HTP after inhibition of cerebral aromatic amino acid decarboxylase by means of NSD-1015 (100 mg.kg-1 i.p.). An increase in catecholamine as well as 5-HT synthesis during sexual activity was observed in both the neostriatum and the nucleus accumbens. An increase in catecholamine synthesis during treadmill locomotion was found in the neostriatum only. No significant changes in monoamine synthesis were found in the septal area or in the anterior hypothalamus.

Animals↗
PubMed1987

The intrinsic activities of the partial dopamine receptor agonists (-)-3-PPP and TDHL on pituitary dopamine receptors are lower in female than in male rats.

The abilities of the mixed agonists/antagonists on dopamine (DA) receptors, (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [-)-3-PPP) and transdihydrolisuride (TDHL), to suppress serum prolactin levels in acutely hyperprolactinemic male and female rats were investigated. gamma-Butyrolactone was used to deplete endogenous DA and raise serum prolactin concentrations. Both (-)-3-PPP and TDHL were found to cause sexually differentiated responses: (-)-3-PPP reduced serum prolactin levels dose dependently and effectively in males but caused only a modest decrease of prolactin release in females. Moreover, (-)-3-PPP antagonized the prolactin-suppressing effects induced by the DA receptor agonist (+)-3-PPP in females. Likewise TDHL decreased prolactin secretion markedly in males while it had only slight effects in females. It can be concluded from these results that the intrinsic activities of the partial DA agonists (-)-3-PPP and TDHL are lower in female than in male rats, suggesting a reduced responsiveness of hypophyseal DA receptors in females. Since DA levels in the pituitary portal circulation are higher in female than in male rats, this study gives further support to the hypothesis claiming an inverse relationship between the intrinsic activity of a mixed agonist/antagonist and the degree of previous stimulation of its receptor.

Animals↗
PubMed1987

HPLC-EC analysis of catechols and indoles in rat brain dialysates.

This short article reviews HPLC-EC methodology that we are currently applying to measure DA, 5-HT and their acid metabolites in rat brain dialysates collected in vivo. HPLC-EC systems based on standard-bore HPLC columns are described which are sufficiently sensitive to allow detection of the monoamine transmitters and their metabolites in regional brain dialysates collected at 10-20 min intervals. A large reduction in sample requirement was achieved by "down-scaling" the conventional HPLC-EC assay to incorporate small-bore HPLC columns. The small-bore systems allowed monoamines to be detected in samples collected over 1 to a few minutes.

Animals↗
PubMed1987

Injection of capsaicin into the nucleus raphe dorsalis elicits heat loss in the rat.

The acute thermoregulatory effect of microinjection of capsaicin into the nucleus raphe dorsalis (NRD) has been studied in anesthetised rats. Application of capsaicin (20 micrograms) into the NRD increased the tail skin temperature and decreased the body temperature. In animals that had previously been treated with capsaicin (50 mg/kg s.c.) the thermolytic effect of capsaicin microinjection was completely abolished. Additionally, the effects of NRD capsaicin injection on the monoamines in the preoptic region + hypothalamus (RPO-H) were studied. Levels of noradrenaline, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by means of liquid chromatography. Neurochemical analysis of RPO-H showed no changes in the serotonin metabolism, but an elevated DOPAC level 30 min after the injection of capsaicin into the NRD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Postsynaptic dopamine (DA) receptor stimulator properties of the putative DA autoreceptor-selective agonist B-HT 920 uncovered by co-treatment with the D-1 agonist SK&F 38393.

Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation--particularly focused stereotyped licking and sniffing--in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha 2-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Anxiolytic-like action of the 3-PPP enantiomers in the Vogel conflict paradigm.

The effect of the (+)- and (-)-enantiomers of 3-PPP [conventional and atypical dopamine (DA)-receptor active agent, respectively] were investigated in a commonly used animal model of anxiety: the Vogel licking-conflict test. Low doses (less than or equal to 0.5 mg/kg SC) of both 3-PPP enantiomers resulted in anti-conflict (= anxiolytic-like) actions in this test. (-)-3-PPP proved to be almost as potent as apomorphine in releasing the punished responding (minimum effective doses; (-)-3-PPP: 0.016, and apomorphine: 0.006 mg/kg SC), whereas (+)-3-PPP was about 10 times less effective than apomorphine. In the higher dose range (greater than or equal to 1.0 mg/kg), both 3-PPP enantiomers instead induced an apparent "pro"-conflict effect; i.e. decreased responding to a level significantly below baseline, thus resulting in a biphasic dose-response curve. Simple alterations in the animals' motivation to drink, in shock threshold or in motor capabilities did not seem to be major explanatory factors either for the anti- or for the "pro"-conflict effects. With regard to the latter, the possibility is discussed of an interaction between the experimental test situation and non conflict-related effects of the drugs, thus interfering with the punished drinking. The findings are interpreted within the concept that low doses of the 3-PPP enantiomers, in particular (-)-3-PPP, may attenuate anxiety-elicited increases in the neurotransmission in certain meso-cortical/limbic DA pathways, i.e. consistent with the previously shown preferentially "limbic" net antidopaminergic profile of action of (-)-3-PPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Lack of effect of moderate hypercalcemia on gonadotropin responsiveness to GnRH.

To investigate whether moderate exogenous hypercalcemia influences the release of gonadotropin from human gonadotrophs, 6 normal men were given 50 micrograms GnRH iv on two occasions. On one of these occasions GnRH was administered on an iv background infusion of calcium gluconate, on the other GnRH was injected on a background infusion of saline. The calcium infusion induced moderate hypercalcemia (2.7-2.9 mmol/l) during the GnRH stimulation, whereas normocalcemia prevailed (2.1-2.2 mmol/l) when saline was infused over an identical time period. Similar FSH and LH responses to GnRH were obtained during normo- and hypercalcemia. Moreover, serum testosterone (T) and estradiol (E2) remained unchanged by the hypercalcemia. These results imply that moderate exogenous hypercalcemia does not affect hormone release from pituitary gonadotrophs, and fails to affect peripheral cells involved in the production of T and E2.

Adult↗
PubMed1987

The Ca++-antagonist nimodipine decreases and the Ca++-agonist Bay K 8644 increases catecholamine synthesis in mouse brain.

The effects of the Ca++-antagonist nimodipine and the Ca++-agonist Bay K 8644 on brain catecholamine synthesis in male albino mice were investigated in vivo. Nimodipine caused a dose-dependent reduction in the synthesis rate of dopamine and noradrenaline, measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of the L-aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine (NSD 1015). In contrast, Bay K 8644 caused an increase in DOPA synthesis. Furthermore, Bay K 8644 dose-dependently antagonized the effect of nimodipine. It is suggested that nimodipine and Bay K 8644 induced these changes by interfering with neuronal Ca++ transport, thus arguing for a role of voltage operated Ca++ channels in normal nerve function.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Dopamine autoreceptor antagonists: effects on sleep-wake activity in the rat.

The effects of the putative dopamine (DA) autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, and cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, on sleep-wake activity, EEG, and motor activity in the rat were studied. Both drugs induced a dose-dependent increase in wakefulness (W) and a reduction in non-REM sleep (NREMS). A definite tendency to a suppression of REM sleep (REMS) could also be observed. The results of spectral analysis indicated that EEG slow wave activity, a marker of sleep intensity, was particularly sensitive to the drugs. Slight differences between the two drugs were observed: (+)-AJ 76 seemed to be more efficacious than (+)-UH 232 in stimulating motor activity. (+)-UH 232 tended to suppress slow wave activity more strongly than (+)-AJ 76. It is suggested that the increase in W following administration of (+)-AJ 76 resulted predominantly from locomotor activation, while (+)-UH 232 might also act on dopaminergic mechanisms involved in the regulation of sleep.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Resolved cis- and trans-2-amino-5-methoxy-1-methyltetralins: central dopamine receptor agonists and antagonists.

A series of 35 stereochemically well-defined C1-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized. The compounds were tested for central DA receptor agonistic and antagonistic activity, by use of biochemical and behavioral tests in rats. In addition, the compounds were tested for in vivo interactions with 5,6-dihydroxy-2-(di-n-propylamino)tetralin (DiPr-5,6-ADTN). On the basis of pharmacological activity profiles, the active compounds have been classified into four groups: classical pre- and postsynaptic DA receptor agonists, DA receptor agonists with preferential action at presynaptic receptors, pre- and postsynaptic DA receptor antagonists, and DA receptor antagonists with preferential action at presynaptic receptors. Results obtained indicate that both 2R and 2S enantiomers of C5-oxygenated 2-aminotetralins may be able to bind to DA receptors but that only 2S antipodes are able to activate the receptors. O-Methylation of the C5-oxygenated (1S,2R)-2-amino-1-methyltetralin derivatives tends to increase their DA receptor antagonistic activity, whereas decrease of the size of the N-substituent(s) from n-propyl to ethyl or methyl appears to increase their activity at postsynaptic DA receptors.

Animals↗
PubMed1987

C3-methylated 5-hydroxy-2-(dipropylamino)tetralins: conformational and steric parameters of importance for central dopamine receptor activation.

C3-Methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations (MMP2). The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (2R,3S)-5-Hydroxy-3-methyl-2-(di-n-propylamino)tetralin [(-)-8] was demonstrated to be a highly potent DA receptor agonist, while the other new compounds were of low potency or inactive. Results obtained confirmed the hypothesis that the tetralin inversion angle phi and the direction of the N-electron pair (N-H) tau N are conformational parameters of critical importance for DA D2 receptor activation in the 2-aminotetralin series. The high potency of (-)-8 allowed an extension of a previously defined "partial DA D2 receptor excluded volume".

Animals↗
PubMed1987

Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b- octahydrobenzo[f]quinoline : central serotonin stimulating properties.

cis-10-Hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b -octahydrobenzo[f]quinoline (4) is a centrally acting serotonin (5-HT) receptor agonist of moderate potency. Due to its semirigid character and the obvious similarity between (4aR,10bS)-4 and more potent, centrally acting 5-HT receptor agonist cis-(1S,2R)-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (2), we carried out the preparation (via resolution of 6, a precursor of 4) and the pharmacological testing of the enantiomers of 4. We were able to show that the active enantiomers of 4 and 2 coincide in terms of stereochemistry, i.e., that it is the 4aR,10bS enantiomer of 4 that is the more active one. The absolute configuration was assigned on the basis of single-crystal X-ray analysis of the precursor (+)-6 of the active enantiomer (-)-4. Conformational analysis with molecular mechanics (MM2) calculations were performed on the N-methyl analogues of compounds cis-(1S,2R)-2 (cis-(1S,2R)-3) and cis-(4aR,10bS)-4 (cis-(4aR,10bS)-7). Both ammonium and free amine forms were subjected to these calculations. The results show a preference for the N-equatorial conformation, which is corroborated by the X-ray structure of (+)-6.HCl. The relatively low potency of compound cis-(4aR,10bS)-4 might be explained by unfavorable direction of the N-lone pair (or ammonium hydrogen) bond in this compound as compared to cis-(1S,2R)-2 and trans-(4aR,10bR)-5, which can be predicted to be the more active enantiomer of compound 5.

Animals↗
PubMed1987

C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors.

C1- and C3-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) have been synthesized, and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics (MMP2) calculations. The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (1S,2R)-7-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin [(+)-10] was demonstrated to be sevenfold less potent than (2R)-7-OH-DPAT as a DA receptor agonist. The other new compounds were of lower potency or inactive.

Animals↗
PubMed1987

(+)-cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin: a potent and highly stereoselective 5-hydroxytryptamine receptor agonist.

C1-Methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1) were synthesized and tested for central 5-HT and dopamine receptor activity by use of a biochemical test method in rats. cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin (8) was found to be a 5-HT receptor agonist. The (+)-enantiomer of 8 had a potency equal to that of 1, whereas (-)-8 and the trans isomer (+/-)-9 were inactive.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

N-substituted 1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines and 3-phenylpiperidines: effects on central dopamine and sigma receptors.

N-Substituted analogues of trans-7- and trans-9-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline (trans-7- and trans-9-OH-OHBQ) were tested for dopamine (DA) D2 receptor affinity by using in vitro [3H]spiperone and in vivo 5,6-di-n-Pr-ADTN binding assays. Potencies at central pre- (auto-) and postsynaptic DA receptors were determined by a biochemical and a behavioral method, respectively. Corresponding data were included for analogous, resolved 3-(3-hydroxyphenyl)piperidines and a few other substituted, racemic 3-phenylpiperidines. Beside the central dopaminergic effects of these compounds, previously reported sigma receptor affinity data [[3H]-(+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine; [3H]-(+)-3-PPP] were also taken into account for a comparison of the structure-activity/affinity relationships of these compounds at these two receptor types. Larger N-substituents in both phenylpiperidines and OHBQs increase both pre- and postsynaptic dopaminergic activity. An n-propyl group gives high dopaminergic efficacy at both receptor sites (pre- and postsynaptic) in all series. However, even higher dopaminergic potency is observed for trans-7-OH-OHBQs and (S)-3-(3-hydroxyphenyl)piperidines with N-substituents larger than n-propyl. In contrast, trans-4-n-Bu-9-OH-OHBQ is inactive, and (R)-3-(3-hydroxyphenyl)-N-n-butylpiperidine is less active at central DA receptors than its corresponding n-propyl analogue. This implies interesting differences in N-substituent sensitivity for the different classes of compounds with respect to the direction of their respective N-substituents at the drug-receptor interaction. The stereochemical and steric demands for sigma receptor affinity are much less stringent. The general trend is that, up to a certain size, the more lipophilic the N-substituent, the higher the affinity for sigma receptor sites.

Animals↗
PubMed1987

Turnover of dopamine and dopamine metabolites in rat brain: comparison between striatum and substantia nigra.

Measurements of the turnover of dopamine (DA) and DA metabolites have been performed in the striatum and substantia nigra (SN) of the rat. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid have been assessed from the disappearance rates after blocking their formation by inhibition of monoamine oxidase by pargyline and of catechol-O-methyltransferase by tropolone. DA turnover has been measured as 3-methoxytyramine (3-MT) plus DA accumulation rate after MAO inhibition by pargyline and as accumulation rate of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of aromatic amino acid decarboxylase by NSD 1015 or NSD 1034. These measures of DA turnover have been compared with alpha-methyl-p-tyrosine (alpha-MT)-induced DA disappearance rate. In SN all the different measures of DA turnover are in the same range (55-62 nmol/g protein/h) whereas in striatum DOPA accumulation rate after NSD 1015 and alpha-MT-induced DA disappearance rate (16-23 nmol/g/h) are much lower than DOPAC disappearance rate after pargyline, 3-MT plus DA accumulation rate after pargyline, and DOPA accumulation rate after NSD 1034 (39-46 nmol/g/h). The data confirm our previous findings indicating that the fractional turnover rate of DA is more rapid in SN than in striatum and that O-methylation of DA is relatively more important in SN. In striatum at least two pools of DA with different turnover rates appear to exist, whereas in SN, DA behaves as if located in a single compartment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Vibration white finger: a follow up study.

To study the course of vibration white finger (VWF) 55 men were re-examined three and a half to six years after the first examination. The patients were interviewed and finger systolic pressure after general body and local finger cooling was measured. The test results at the two examinations were compared. At the follow up examination some patients experienced a subjective improvement of VWF symptoms but not until more than three years had passed after they had stopped working with vibrating tools. To study the effect of diminished cold exposure on subjective symptoms, vibration exposed outdoor workers who changed to unexposed indoor work were studied separately. In this subgroup also improvement was reported only when more than three years has passed after the change of work, indicating that diminished cold exposure is not the primary explanation for the improvement. The cold provocation test, however, showed no tendency towards a diminished reaction of the vessels to cooling. Patients who continue to work with vibrating tools report a subjective increase in symptoms. This subjective impairment was reflected in an increased reaction to cold as measured in the cold provocation test.

Adult↗