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Biomedical subjects

S B Ross

Publications and source records attributed to S B Ross.

At least 127 records · Page 7Linked to original sources
PubMed1982

Serotonin involvement in aversive conditioning: reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a serotonin (5-HT) agonist, fenfluramine and p-chloroamphetamine (PCA), which are 5-HT releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. Depletion of central 5-HT neurones after long-term PCA treatment (2 X 10 mg/kg) completely blocked the retention impairment resulting from acute PCA (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-MeO-DMT (4 mg/kg). 5-HT depletion after p-chlorophenylalanine (PCPA) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-HT stores in the action of PCA and PCPA. These data further underline the importance of the ascending 5-HT pathway in aversive conditioning in the rat.

Amphetamines↗
PubMed1982

On the role of the dorsal mesencephalic tegmentum in the control of masculine sexual behavior in the rat: effects of electrolytic lesions, ibotenic acid and DSP 4.

The work presented here concerns the way in which the dorsal midbrain tegmentum (DMT) participates in the control of sexual behavior. It was first established that electrolytic DMT lesions accelerate mating in the male rat, primarily by abbreviating the post-ejaculatory interval. Since the effective lesions were accompanied by decreases in the in vitro synaptosomal uptake of [3H]noradrenaline (NA) in hippocampus and hypothalamus, the behavioral effects of DSP4 (which elicits degeneration in NA nerve terminals derived primarily from the locus coeruleus) were examined. The long-term behavioral consequences of DSP4, however, were to decrease copulatory rate despite substantial NA denervation of brain and spinal cord. Ibotenic acid-induced neuronal degeneration in the DMT, on the other hand, accelerated copulatory behavior while leaving NA innervation of hippocampus and hypothalamus unaffected. The magnitude of the behavioral effect in ibotenic acid-treated rats was less than that induced by electrolytic DMT lesions. It is tentatively suggested on the basis of these-experiments that DMT cell bodies may form part of a system regulating sexual arousal mechanisms, whilst activity in a non-adrenergic fiber system running in the dorsal tegmental bundle may be required for active inhibition of sexual behavior after ejaculation. In additional experiments it was found that DSP4 treatment of female rats produced negligible effects on sexual behavior, estrous cyclicity and processes related to lactation.

Amines↗
PubMed1982

(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)), a selective inhibitor of the A form of monoamine oxidase in the rat brain.

(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)) and its N-demethylated secondary amino derivative FLA 788(+) were examined for their monoamine oxidase (MAO) inhibitory effects in the rat brain. They were found to be reversible and very selective inhibitors of the A form of monoamine oxidase in vitro and in vivo after oral administration. FLA 788(+) was 2-6 times more active than FLA 336(+) in vitro depending on the assay technique employed but the two compounds had similar potency after oral administration. Both compounds inhibited competitively the deamination of 5-hydroxytryptamine by hypothalamic mitochondria. Although the irreversible inhibitor clorgyline was 60 times more potent than FLA 336(+) in vitro, it was equipotent with FLA 336(+) and FLA 788(+) in the rat brain after oral administration. There was a high correlation between the log plasma concentration of FLA 788(+) and the MAO inhibition in hypothalamic slices. The plasma concentration of the metabolite FLA 788(+) exceeded that of FLA 336(+) after oral administration of the latter compound. Thus, the MAO inhibition produced by FLA 336(+) in vivo, appears in part to be due to the metabolite FLA 788(+).

Animals↗
PubMed1982

DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion.

N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following administration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2 x 30 mg/kg IP) was not found to cause any avoidance impairment, although its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance acquisition is mediated via central, and not peripheral NA neurons.

Amines↗
PubMed1982

Selective inhibition of the A form of monoamine oxidase by 4-dimethylamino-alpha-methylphenylalkylamine derivatives in the rat.

The inhibitory effects on monoamine oxidase (MAO) of some dimethylamino-alpha-phenylalkylamine derivatives were examined in a rat brain mitochondrial preparation in vitro and in rat brain slices following oral administration. In the in vitro assay the compounds were shown to be selective inhibitors of the A form of MAO, being 100-600 times more potent in inhibiting the deamination of [14C]5-hydroxytryptamine than that of [14C]phenetylamine. Using an ex vivo brain slice technique it was found that the new compounds were reversible and very selective inhibitors of type A MAO in the rat brain and the most potent compounds (FLA 405, 314, 336 and 558) were equipotent with clorgyline. The compounds increased the monoamine concentrations in whole rat brain, particularly that of 5-hydroxytryptamine, in the same dose range which produced MAO inhibition. Some of the new compounds, e.g. FLA 336 and FLA 717, caused only weak potentiation of the vaso-pressor effect of orally administered tyramine.

Animals↗
PubMed1982

A double-blind study of zimelidine, a serotonin uptake inhibitor, and desipramine, a noradrenaline uptake inhibitor, in endogenous depression. II. Biochemical findings.

In a comparative evaluation of zimelidine, a potent serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, 65 hospitalized patients with endogenous depression were evaluated for the following biochemical variables: 5-HT uptake in platelets, 5-HT concentration in whole blood, inhibition of the 5-HT and NA accumulation in rat hypothalamic synaptosomes incubated in the patients' plasma, the excretion of 4-hydroxy-3-methoxyphenyl glycol (HMPG) in urine and the pretreatment levels of the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and HMPG in cerebrospinal fluid (CSF). results of the biochemical studies confirmed that zimelidine and desipramine have different profiles with respect to monoamine uptake. Thus zimelidine caused more marked inhibition of 5-HT uptake than desipramine, especially in rat brain synaptosomes incubated in the patient's plasma. Desipramine plasma was much more effective than zimelidine plasma in inhibiting NA uptake in the same preparation. The urinary excretion of HMPG decreased significantly during desipramine treatment but remained unchanged during zimelidine treatment. The combined clinical and biochemical results indicated that patients with low pretreatment levels of 5-HIAA and HVA in CSF responded significantly better to zimelidine than patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of HMPG in CSF tended to respond better to desipramine than those with low levels of this NA metabolite.

Adult↗
PubMed1981

Regional in vivo binding of [3H]N-propylnorapomorphine in the mouse brain. Evidence for labelling of central dopamine receptors.

Tail vein injections of [3H]N-propylnorapomorphine ([3H]NPA) in male mice resulted in a dose-related accumulaton of radioactivity in the following brain regions: striatum (max), olfactory tubercle and cerebellum (min). The specific binding was saturable with increasing concentrations of the drug and stereospecifically displaced by (+) butaclamol. Dopamine agonist (apomorphine, NPA and bromocriptine) and antagonists (spiperone, haloperidol, (+) butaclamol and I-sulpiride) all caused dose-dependent prevention of [3H]NPA binding. Mianserin, phenoxybenzamine and propranolol did not prevent the in vivo [3H]NPA binding suggesting that [3H]NPA binds specifically to dopamine receptors in the striatum and the olfactory tubercle of the mouse.

Animals↗
PubMed1981

Effects of zimelidine and desipramine on serotonin and noradrenaline uptake mechanisms in relation to plasma concentrations and to therapeutic effects during treatment of depression.

The selective inhibitors of neuronal 5-hydroxytryptamine (5-HT) and noradrenaline (NA) uptake, zimelidine and desipramine, were compared in a double blind crossover study of 40 inpatients with endogenous depression. The clinical effects of these two drugs and some biochemical variables related to the monoamine systems were studied during 4 weeks' treatment. Patients with a low pretreatment level of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (less than 20 ng/ml) responded significantly better to zimelidine treatment than those with a high pretreatment level (greater than 20 ng/ml). In the group treated with desipramine no difference in therapeutic outcome was obtained between patients with low and high pretreatments levels of 5-HIAA in the CSF. Attempts to correlate the steady state plasma concentrations of zimelidine, norzimelidine and desipramine with the therapeutic effect were unsuccessful. The plasma concentration of norzimelidine demonstrated a significant (P less than 0.05) positive correlation with age. The mean value of the uptake of 14C-5-HT in the patient's platelets, when measured before the treatment, was significantly (P less than 0.05) lower than found in a control group. Zimelidine, mainly via its metabolite norzimelidine, caused a pronounced inhibition of uptake of 14C-5-HT in platelets, decrease in whole blood 5-HT and inhibition of accumulation of 14C-5-HT in rat hypothalamic synaptosomes incubated in the patients plasma. Desipramine produced a slight inhibition of accumulation of 14C-5-HT in rat synaptosomes, but a marked inhibition of uptake of 14C-5-HT in the patient's platelets and a decrease in whole blood 5-HT. The accumulation of 3H-NA in rat synaptosomes incubated in the patient's plasma was strongly inhibited by desipramine treatment but only slightly affected by zimelidine.

Animals↗
PubMed1981

Synthesis of pyridylallylamines related to zimelidine and their inhibition of neuronal monoamine uptake.

Analogues of the antidepressant agent zimelidine [6, (Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine], a selective inhibitor of neuronal 5-hydroxytryptamine reuptake, were synthesized by several routes with the aim of obtaining compounds having a cis configuration (with respect to pyridyl and allylamine). Two methods utilized suitably substituted benzoylpyridines as starting materials. In two other routes, the bromine in 6 was either directly displaced (CN) or converted via the corresponding lithio derivative to H, Cl, I, Me, SiMe3, and SMe. The configurations were determined by UV, 1H NMR, and lanthanide-induced shifts in 1H NMR. The compounds were evaluated as uptake inhibitors by measuring the accumulation of [3H]noradrenaline and 5-hydroxy[14C]tryptamine in mouse brain slices (in vitro and in vivo). Para substitution favored 5-hydroxytryptamine activity and ortho substitution favored NA activity in the cis series. The in vitro effect on 5-hydroxytryptamine was rather insensitive to variations in the para substituent, whereas pronounced effects in vivo were observed only with Cl, Br (6), and I.

Animals↗
PubMed1981

Erythrocyte catechol-O-methyltransferase activity in a Swedish population.

Erythrocyte catechol-O-methyltransferase (COMT) activity has been analyzed in 185 individuals. The activities showed a trimodal frequency distribution. This suggests an autosomal codominant inheritance of the human erythrocyte COMT activity. The mean male COMT activity was 18.9 +/- 7.0 (S.D.) nmol/ml RBC/h. The mean female activity was 16.1 +/- 6.3 nmol/ml RBC/h and the frequency distribution pattern for women was shifted towards lower values.

Adult↗
PubMed1981

Kinetic aspects of monoamine oxidase activity in twins with psychoses.

Monoamine oxidase activity was assayed in platelets from 22 (8 monozygotic and 14 dizygotic) twin pairs. At least one twin of each pair had a serious psychiatric disorder (proband). Phenethylamine was used as substrate and the assay was performed at two different oxygen concentrations (0.06 and 0.12 nM). Apparent Km and Vmax values were estimated from double reciprocal plots. The correlation between proband and control twins was high for both apparent Km (r = 0.83) and Vmax (r = 0.69) when the enzyme was assayed at the higher concentration of oxygen. The monozygotic twins pairs showed very high correlations (Km r = 0.93; Vmax r = 0.86) as compared to dizygotic twins (Km r = 0.81, Vmax r = 0.50) and apparently healthy subjects (Km r = 0.46, Vmax r = 0.33). No difference in kinetic properties was found between schizophrenic and non-schizophrenic twins.

Blood Platelets↗
PubMed1981

Plasma dopamine beta-hydroxylase activity in a North Swedish isolate with a high frequency of schizophrenia.

Plasma dopamine beta-hydroxylase (DBH) activity was determined in 115 members of a North Swedish geographical isolate with a high frequency of schizophrenia, of which 30 persons had schizophrenia, and was compared with a Middle Swedish population of 185 apparently healthy persons. There was no significant difference between the schizophrenic group and their healthy relatives or between the North and Middle-Swedish populations. The number of persons with very low plasma DBH activity in the North Swedish population appeared to be less than those in the control population.

Dopamine beta-Hydroxylase↗