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Biomedical subjects

S Algeri

Publications and source records attributed to S Algeri.

At least 37 records · Page 2Linked to original sources
PubMed1987

Modulation of striatal dopamine metabolism by the activity of dorsal raphe serotonergic afferences.

Serotonin (5-HT)-dopamine (DA) interaction was studied in the caudate nucleus after electrical stimulation of the dorsal raphe (DR), an area containing 5-HT cell bodies and sending afferences to nigrostriatal dopaminergic neurons. The DR was stimulated by means of a bipolar stainless steel electrode for 16 min (10 Hz, 0.6 ms, 200 microA). 5-HT and DA metabolism were monitored before, during and after stimulation by in vivo differential pulse voltammetry. This electrochemical technique uses carbon fiber electrodes implanted in brain areas to record oxidation peaks corresponding to extracellular 5-hydroxyindolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC). Changes in the concentrations of the metabolites were recorded every 2 min in freely moving rats. Both 5-HIAA and DOPAC increased in the first minutes after the beginning of stimulation, the rise lasting 30 min after the end. That DR was closely involved was borne out by the fact that stimulation in the surrounding areas had no effect on either metabolite. Classical biochemical determinations in tissue samples were also used to study the effect on DA release: 3-methoxytyramine (3-MT) levels, measured in basal conditions and after blockade of its degradation by pargyline, were not changed, indicating that DR stimulation, though increasing DA metabolism, does not affect release. However, modulation of DA transmission by 5-HT afferences seems possible in certain circumstances. This 5-HT-DA interaction appears to be presynaptic (on dopaminergic terminals or cell bodies) since it is not prevented by kainic acid degeneration of striatal neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified by in vivo voltammetry.

Differential pulse voltammetry with carbon fiber electrodes was used to study serotonin (5-HT) metabolism in freely moving rats. The electrodes implanted in the striatum recorded the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak after oral tryptophan (150 mg/kg). This 5-HT precursor did not modify the 5-HIAA peak in any rat tested, but it raised 5-HIAA levels determined in total tissue by a classical biochemical method (HPLC). The administration of 5-hydroxytryptophan (5-HTP) (25 mg/kg i.p.) induced an increase of 5-HIAA detectable both in the extracellular medium by voltammetry and in tissue samples. As previously shown, dorsal raphe electrical stimulation raises extracellular 5-HIAA in the striatum and this effect is enhanced by pretreatment with tryptophan. The results suggest that tryptophan in 'normal' conditions enhances 5-HT metabolism without affecting 5-HT release unless such release is stimulated. 5-HTP increases 5-HT metabolism and release.

Animals↗
PubMed1987

Different toxicity of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the nigrostriatal and mesolimbic pathways.

The influence of MPTP (30 mg/kg X 2) on dopamine content and tyrosine hydroxylase activity in striatal, limbic and cortical areas of C-57/B16 mice was studied. General dopamine depletion was observed 24 h after the treatment, but 30 days after administration recovery was complete in all but the striatum. At 24 h, tyrosine hydroxylase activity was decreased only in striatum. It is proposed that MPTP acts differently in striatum and in other dopaminergic areas.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Biochemical and behavioural indices of striatal dopaminergic activity after 6-methyltetrahydropterin.

The biochemical effects of 6-methyltetrahydropterin (6-MPH4), a synthetic analogue of tetrahydrobiopterin (BH4), the hydroxylase cofactor, were investigated on striatal dopaminergic neurons in the rat. Although a single parenteral dose of 6-MPH4 (18 or 54 mg/kg) did not significantly increase the content of dopamine (DA) or its acidic metabolites, L-didrohyphenylanine (L-DOPA) accumulation after decarboxylase inhibition was evident in rats receiving 54 mg/kg of 6-MPH4. On the other hand, 6-MPH4 (18 mg/kg) potentiated the reserpine-induced DA metabolism as demonstrated by increased HVA levels. In a behavioural test, 6-MPH4 partially prevented haloperidol-induced catalepsy. BH4 concentrations could thus be subsaturating with respect to tyrosine hydroxylase (TH), particularly when the enzyme activity is stimulated and the results suggest that cofactor supply may have pharmacological significance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Behavioural and biochemical studies on 6-methylamino-4,5,6,7-tetrahydrobenzothiazole (14.839JL), a new potent dopaminergic agonist.

6-Methylamino-4,5,6,7-tetrahydrobenzothiazole monochlorhydrate (14.839JL) is a new, potent dopaminergic agonist. The stereotypy induced by this drug was greater than that induced by an equivalent dose of apomorphine, was antagonized by pretreatment with sulpiride and counteracted the hypomotility induced by reserpine. Striatal levels of the dopamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were significantly lowered for up to 4-6 h by doses from 0.05 to 1 mg/kg. The drug was also very effective in lowering prolactine secretion. 14.839JL displaced [3H]N-n-propylnorapomorphine [3H]NPA from striatal binding sites with an IC50 similar to dopamine (DA). Conversely, the ability of 14.839JL to displace 3H spiperone from its binding sites was 100 and 10 times lower than that of haloperidol and sulpiride, and similar to that of SCH 23390. Differently from the latter, however, 14.839JL did not modify adenylate cyclase activity. All these data suggest that 14.839JL is a new, potent, long-lasting direct DA agonist, probably acting on D2 receptors.

Adenylyl Cyclases↗
PubMed1986

Differences in the effect of the antidepressant amineptine on striatal and limbic DOPAC measured by HPLC-ECD and in vivo voltammetry.

The acute effect of the antidepressant amineptine was studied in two dopaminergic areas, the striatum and the limbic system, by in vivo voltammetry. This electrochemical technique uses carbon fibre electrodes implanted in brain areas of non-anaesthetized freely moving rats to measure DOPAC diffusing from the neurons. In vivo voltammetry recordings showed that amineptine induced a slight and transient decrease in DOPAC levels in the caudate nucleus but a persistent, clear-cut decrease in the nucleus accumbens. These results were confirmed by classical biochemical determination in tissue samples. The findings indicate the possible importance of the limbic area in the mechanism of action of amineptine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Effects of sustained hyperprolactinemia induced by chronic treatment with domperidone on central dopaminergic systems in the rat.

Chronic treatment with Domperidone (DOM) had no effect on basal prolactin (PRL) secretion or basal levels of Dopamine (DA) metabolites in basal hypothalamus and striatum as compared with the vehicle treated rats. Animals chronically treated with DOM did not present tolerance to a challenge dose of Haloperidol (HAL) and DOM either measuring PRL secretion or striatal DA metabolite levels. The PRL-induced increase in hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) was reduced. These results were accompanied by no change at striatal DA receptors, a slight reduction in density-affinity at hypothalamic DA receptors but clear-cut modification in pituitary DA receptors with the appearance of a high affinity-low capacity binding sites. It can be surmised that sustained hyperprolactinemia may induce tolerance in hypothalamic Tuberoinfundibular (TIDA) neurons involved in the inhibitory control of PRL secretion and a change in the kinetic properties of pituitary DA receptors, but it does not consistently affect the activity of the nigro-striatal DA system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Stress induced desensitization of lymphocyte beta-adrenoceptors in young and aged rats.

The effects of different times of immobilization stress on intact lymphocyte beta-adrenoceptors and plasma corticosterone were compared in 3-month and 24-month-old rats. In young animals after 30 min restraint 3H-dihydroalprenolol specific binding was significantly reduced (61% of control value) and plasma corticosterone significantly raised (186% of control). The effect on beta-adrenoceptors was due changes in receptor number (Bmax) without any effect on affinity (KD). In aged rats both effects were only seen after 180 min restraint and were less pronounced. Isoproterenol treatment in vitro reduced beta-adrenoceptors on lymphocytes. This effect was less pronounced in lymphocytes from aged rats. Corticosterone in vitro increased 3H-dihydroalprenolol specific binding. We therefore suggest that the decrease of beta-adrenoceptors reflects an adaptive response to the stress-induced catecholamine release and that corticosterone could play a role in reversing this effect. This adaptive response to stress seems to be impaired in aged animals.

Age Factors↗
PubMed1986

Amineptine: its effect on the dopaminergic system of rats.

3-Methoxytyramine formation was enhanced by amineptine (40 mg kg-1 i.p.) in the striatum and limbic area, indicating an increase in the concentration of dopamine in the extraneuronal space. Since dopamine turnover, determined as the rate of L-dopa accumulation, is reduced by the drug at short (10 min) times, the enhanced extraneuronal dopamine concentration seems mainly related to amineptine-induced inhibition of its uptake.

Animals↗
PubMed1985

Cross tolerance between ketamine and morphine to some pharmacological and biochemical effects.

Whether morphine and ketamine induced cross-tolerance to some of their common pharmacological and biochemical effects, namely analgesia and enhancement of metabolites of dopamine (DA) in the striatum and limbic area of the rat was analysed. Ketamine was given at the dose of 100 mg/kg, twice a day for 8 days. After this treatment, a challenge dose of morphine (15 mg/kg, i.p.) still induced analgesia comparable to that induced by morphine alone, showing no cross-tolerance to this effect. In contrast, the challenge dose of morphine given to ketamine-tolerant rats no longer enhanced metabolism of DA, indicating the appearance of cross-tolerance to this effect. A high degree of tolerance to morphine was obtained after the subcutaneous implantation of rats with pellets of morphine; a challenge dose of ketamine to morphine-tolerant rats induced marked analgesia, with no cross-tolerance to this pharmacological effect, while cross-tolerance was present to the biochemical effect. The existence of a high degree of reciprocal cross-tolerance in both areas and on both metabolites of DA is consistent with the hypothesis of action at a common receptor; the lack of cross-tolerance to the analgesic effect indicates that analgesia is achieved by a different mechanism for the two drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Stimulation of serotonin synthesis in rat brain after antiepilepsirine, an antiepileptic piperine derivative.

Piperine and two of its derivatives, antiepilepsirine (AE or 3,4-methylendioxycynnamoylpiperine) and compound 7448 (N-isopropyl 3 (4 chloro-phenyl) propenoylamide) are very effective in stimulating serotonin (5HT) synthesis. AE raises the ratio of free-to-bound tryptophan (TP) in plasma and induces a long-lasting increase of this aminoacid in brain. At the same time in striatum and limbic area it causes a lasting increase in 5 hydroxyindolacetic acid (5HIAA) a 5HT metabolite and to a lesser extent, an increase in the levels of the monoamine itself. Together with this action on 5HT metabolism we found that AE caused release of 3H-5HT from an in vitro synaptosomal preparation. It thus appears that piperine and its derivatives AE and compound 7148 affect the central serotonergic system.

Animals↗
PubMed1984

In vivo and in vitro evidence of dopaminergic system down regulation induced by chronic L-DOPA.

The biochemical modifications which occur in the dopaminergic system after chronic administration of L-DOPA are investigated. Levels of DA and of its metabolite 3-methoxytyramine (3-MT), an expression of the amount of DA released, were raised to the same extent in controls given a single dose of 1-DOPA and in chronically treated rats given 100 mg/kg of 1-DOPA plus 25 mg/kg of benserazide twice a day for 24 days. However, the reduction in neuronal function expressed by the decrease in 3-MT which follows treatment with DA agonists such as piribedil and apomorphine was less pronounced in the chronically L-DOPA treated rats. This suggests that such treatment causes a down regulation of DA receptors. These in vivo results were confirmed by in vitro analysis of DA receptor activity after chronic L-DOPA. Under these conditions there was a significant reduction in the number of [3H]-spiperone and [3H]-ADTN binding sites with no changes in their affinity. The in vivo and in vitro findings both suggest the involvement of a subsensitive compensatory mechanism or down regulation of dopaminergic neurons after chronic treatment with L-DOPA.

Animals↗
PubMed1984

Age-related modification of dopaminergic and beta-Adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine.

Microviscosity of membranes prepared from striata and cortex of 3 or 30-month-old rats was measured by fluorescence polarization and electron spin resonance. The viscosity of the hydrophobic core of the lipid bilayer was significantly increased in striatal but not in cortical membranes of old rats. In old rats the incorporation of methyl groups into phosphatidylcholine was significantly lower than in young rats. beta-Adrenergic specific binding sites were reduced in striata, cortex and pineal gland of old rats. In the striata of these animals, [3H] spiperone specific binding sites and dopamine-stimulated adenylate cyclase were also low. A chronic treatment of old rats with S-adenosyl-L-methionine, the cofactor in phospholipid methylation, lowered microviscosity to normal values in striata but not in the cortex. In the same old rats, the beta-receptor in striata and pineal gland returned towards juvenile values; in the cortex, the modification was in the same direction but did not reach significance. Neither putative dopaminergic receptors nor the adenylate cyclase age-dependent decrease was modified by treatment with S-adenosyl-L-methionine.

Aging↗
PubMed1984

Depletion and recovery of neuronal monoamine storage in rats of different ages treated with reserpine.

The effect of reserpine on dopamine, noradrenaline, adrenaline and serotonin concentrations in different brain regions, and the recovery of normal levels of these monoamines after such treatment were studied in rats aged 5, 15 and 27 months. In a preliminary experiment we found that distribution of the drug was not altered in the aged rats. Then we observed that a single dose of reserpine (5 mg/kg IP) had a similar depleting effect on all the brain monoamines, in all the brain regions considered in all three age groups. The curves expressing recovery of monoamine storage in all the nerve terminals, several days after treatment, were superimposable. These results suggest that in the rat, age does not influence the effect of reserpine on the storage mechanism of brain monoamines. Moreover, as restoration of this mechanism depends on the synthesis of new vesicles, the similarity in the rates of recovery in adult, old and very old rats indicated indirectly that synthesis of these neuronal organelles is not affected by aging.

Aging↗
PubMed1984

Biochemical effects of minaprine on striatal dopaminergic neurons in rats.

The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg-1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytyramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg-1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.

Animals↗
PubMed1983

Does acute L-DOPA increase active release of dopamine from dopaminergic neurons?

L-DOPA is believed to be decarboxylated by the residual striatal dopaminergic presynaptic terminals with formation of the putative neurotransmitter dopamine (DA) and with increased availability of DA at post-synaptic receptors. However there is no direct evidence that the DA formed is released into the synaptic cleft. We therefore investigated the biochemical modifications occurring in the dopaminergic system after acute administration of L-DOPA. After acute L-DOPA (100 mg/kg plus 25 mg/kg of benserazide p.o.) the levels of 3-methoxytyramine (3-MT), a metabolite reflecting release of the neurotransmitter DA, were significantly raised, following the same pattern as DA levels, indicating that DA release from DA nerve terminals is increased after L-DOPA administration. The increased DA release and 3-MT formation were not reduced by pretreatment with direct DA agonists such as apomorphine (5 mg/kg i.p.) or piribedil (120 mg/kg p.o.). Thus in this case DA release is not under the control of the compensatory mechanisms induced by post-synaptic receptor hyperstimulation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Dopaminergic effects of buspirone, a novel anxiolytic agent.

The novel anxiolytic drug buspirone raised striatal levels of the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) 1 hr after oral administration. This effect was dose-dependent with a peak at 60 min. No changes were observed in the levels of 3-methoxytyramine (3MT), the extraneuronal metabolite of dopamine. Noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were not affected. Buspirone displaced [3H]spiroperidol from striatal binding sites, with an IC50 (1.8 x 10(-7) M), comparable to that of clozapine (IC50 = 1.4 x 10(-7) M) but considerably lower than that of haloperidol (4.7 x 10(-9) M). Buspirone was only a weak inhibitor of dopamine-stimulated adenyl cyclase. Buspirone was not active on the binding of trifluoperazine to calmodulin and did not modify calmodulin-induced activation of phosphodiesterase (PDE). Repeated administration of buspirone did not increase the number of DA receptors. These data show that, although buspirone has antidopaminergic activity, it can hardly be classified as a classic neuroleptic agent.

Animals↗