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Biomedical subjects

S Algeri

Publications and source records attributed to S Algeri.

At least 55 records · Page 3Linked to original sources

The effect of opiate treatment on the postdecapitation reflex and monoamine metabolism in the rat spinal cord.

Post-decapitation seizures (PDR) are a spinal reflex which seems regulated by some monoaminergic neurons present in the spinal cord (S.C.). In order to better characterize the role of dopaminergic neurons in PDR, we studied the effect of treatment with opiates, which are known to increase dopamine (DA) and serotonin (5HT) metabolism in the brain, on the duration of PDR and on the metabolism of DA and 5HT in S.C. Morphine, given either IP or ICV, reduced the duration of PDR and increased DA metabolism. Both effects were more evident after systemic administration. [D-Ala2]Met5 enkephalin amide acted similarly to ICV administered morphine. Biochemical and behavioral effects were significantly correlated.

Animals↗

Effects of dopaminergic agents on monoamine levels and motor behaviour in planaria.

1. Dopamine, serotonin and, in lesser amounts, norepinephrine were detected in Dugesia gonocephala using electrochemical detection coupled with liquid chromatography (LCED). 2. Treatment with L-dopa induced hyperkinesias, and a rise in dopamine, serotonin and norepinephrine content, whereas reserpine reduced motor activity and the concentrations of all three monoamines. 3. Haloperidol reduced motor activity and dopamine and norepinephrine levels. 4. Apomorphine induced hyperkinesias without altering monoamine levels.

Animals↗

Simultaneous determination of DA, NA, 5HT and their metabolites in several rat brain areas by HPLC with electrochemical detection.

A simple and rapid method is presented for the determination of serotonin, dopamine, noradrenaline and their metabolites. The method is based on separation of the different compounds by absorption onto A1(2)O3 or organic solvent separation. The compounds extracted are further separated by HPLC and detected electrochemically. Amounts of 5HT, DA, NA and DA metabolites in several brain regions are reported. An account of the relationships between different neuronal systems, the possibility of simultaneously assaying serotonin (5HT) dopamine (DA) and noradrenaline (NA) and their metabolites dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-indolacetic acid (5HIAA) in the same brain area is sometime important for understanding the drugs' effects of mechanisms of action on monoaminergic systems (Ponzio et al., 1981; Holmes and Rutledge, 1976). Therefore we modified our liquid chromatography with electrochemical detection (LCEC) methods for assaying 5HT (Ponzio and Jonsson, 1979), NA and DA (Keller et al., 1976), DOPAC, HVA and 5HIAA (Ponzio and Jonsson, 1978) in order to determine their levels in the same sample.

3,4-Dihydroxyphenylacetic Acid↗

Effects of systemic and intracerebroventricular domperidone treatment on striatal and hypothalamic dopaminergic neurons.

In this study we compared the effects of systemic administration of haloperidol (HAL), a typical dopaminergic antagonist and of domperidone (DOM), a dopamine (DA) receptor blocker which does not cross the blood brain barrier but has a potency similar to HAL at DA receptors, on hypothalamic and striatal DA system turnover (evaluated by means of HVA and DOPAC levels) and prolactin (PRL) secretion in male rats. In accordance with previous data, we found that HAL (1 mg/kg, i.p.) raised DOPAC and HVA levels whereas DOM (1 mg/kg, i.p.) did not alter DA turnover in striatum. Both DOM and HAL affected the hypothalamic DA system, increasing DOPAC levels in a pattern similar to that observed in PRL secretion. An intracerebroventricular (icv) injection of DOM and HAL (4 micrograms/10 microliters/rat) was then made to investigate its effect on DA turnover in this experimental condition at striatal and hypothalamic level. DOM stimulated DA turnover a little in the striatum though its action was delayed; no effects were seen on HVA and DOPAC concentrations in the hypothalamus at any of the tested times. On the other hand, an equal amount of HAL induced an increase in striatal HVA and DOPAC levels, with no significant effects on hypothalamic DA metabolites. These results show that systematically administered DOM and HAL may affect the hypothalamic tuberoinfundibular DA system, probably acting through PRL release. Furthermore DOM, even when injected icv, shows only weak antidopaminergic action on DA turnover in both central areas.

3,4-Dihydroxyphenylacetic Acid↗

Similarities and differences between D-ALA2 MET5 enkephalin amide and morphine in the induction of tolerance to their effects on catalepsy and on dopamine metabolism in the rat brain.

Rats were made tolerant to morphine or to DALA, a synthetic analogue of met-enkephalin, by prolonged exposure to these compounds. Tolerance was assessed by evaluating the resistance of the treated rats to present catalepsy after an acute dose of the opiates. Both morphine and DALA induced tolerance and cross-tolerance to the cataleptic effect. Acute administration of morphine and DALA increased the concentration of DOPAC in striatum, limbic area and s.nigra of control rats. This increase was not present when morphine was given acutely to chronically morphine-treated rats, indicating that these animals were tolerant to this effect. Chronically morphine-treated rats given DALA presented partial tolerance to the biochemical effect of the peptide in limbic area and in s.nigra but not in striatum, indicating that only in certain areas was cross-tolerance produced by chronic morphine. When DALA was administered at different doses to chronically DALA treated rats, the peptide induced rise in DA catabolite was similar to that produced in control animals, so clearly there was no tolerance to this biochemical effect. In these animals cross tolerance to morphine's effect on DA metabolism was present in s.nigra but not in the other two areas, indicating that s.nigra is particularly sensitive to opiate-induced tolerance on DA metabolism.

3,4-Dihydroxyphenylacetic Acid↗

Changes with age in rat central monoaminergic system responses to cold stress.

Changes with age in responses to stress of certain central monoaminergic systems were investigated. Three groups of rats, 4, 18 and 29 months old, were exposed to cold and the effect of this stress on hypothalamic tyrosine hydroxylase, and on the metabolism of DA and 5HT in different brain regions was evaluated. Senescent rats were unable for several hours to compensate the loss of body heat. Corticosterone secretion however was equally stimulated. Hypothalamic tyrosine hydroxylase activity was enhanced in the young rats but not in the old ones. However, the two groups of senescent rats did not show the increase in HVA levels noted in striata of young rats 2 hours after cold exposure. In contrast, the 18 and 29-month-old rats presented enhanced serotonergic tonus, indicated by the greater increase in 5HIAA determined by stress.

Aging↗

Changes in monoamines and their metabolite levels in some brain regions of aged rats.

The concentrations of dopamine (DA) norepinephrine (NE), serotonin (5HT) and their metabolites, HVA, DOPAC, MHPG-SO4 and 5HIAA were measured in several brain areas of rats aged 4, 18 and 29 months. Dopamine and its metabolites showed a decline, statistically correlated with age, in all the dopaminergic areas considered, indicating that this system is profoundly affected in the senescent rat. The changes in the noradrenergic system were more complex. This neurotransmitter was reduced in spinal cord and in limbic area, but was not modified in hippocampus, cerebellum, striatum and s. nigra. In cortex, MHPG-SO4, the main NE metabolite, showed a significantly age-related increase. Tyrosine hydroxylase (TH) activity was low in striatum, and brainstem but not in hypothalamus of aged rats. Neither 5HT nor its metabolites was affected by age. The results indicate that central catecholaminergic systems are markedly affected in senescent rats.

3,4-Dihydroxyphenylacetic Acid↗

D-L-tetrahydropalmatine as monoamine depletor.

D-L-Tetrahydropalmatine (THP), an alkaloid found in the plants of the Carydalis species, has been used as a non-narcotic analgesic and immediate or short-acting hypnotic. The drug's biochemical effects on the rat monoaminergic neuronal system were studied and the findings are presented here. THP's effects on concentrations of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were determined. In all cases the drug caused a depletion of these transmitters. DA was most markedly affected by treatment (-70%), followed by NA (-50%) and 5-HT (-30%). In parallel with the reduced concentrations of the transmitters there was an increase in their acid and neutral metabolites: HVA and DOPAC for DA, 5HIAA for 5-HT and MHPG-SO4 for NA, indicating that THP increases the release of the monoamines. The concentration of 3-methoxytyramine, an extraneuronal metabolite of DA, was, however, reduced suggesting that the observed increase in metabolism is only an intraneuronal phenomenon and that the release of the neutotransmitter is actually impaired. The effect of THP on the peripheral adrenergic system was also determined. NA stores in heart sympathetic nerves were depleted, but the drug had no effect on the adrenaline content of adrenal glands. The biochemical action of THP seems, therefore, to be similar to that of reserpine-like drugs.

3,4-Dihydroxyphenylacetic Acid↗

Differential effects of certain dopaminergic drugs on the striatal concentration of dopamine metabolites, with special reference to 3-methoxytramine.

Studies were undertaken to evaluate the effect of certain dopamine (DA) agonists and antagonists on DA metabolite concentrations in rat striatum, with special regard to 3-methoxytyramine (3-MT). Quipazine, nomifensine and piribedil act as dopaminergic agonist drugs. However piribedil, which is a dopaminergic receptor agonist, reduced the concentrations of all 3 metabolites considered, while nomifensine produced an increase, and quipazine caused an early rise in 3-MT followed by a lowering of the concentration of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Haloperidol and clozapine are both DA antagonists. Haloperidol, which blocks DA receptors, caused an increase in the formation of all 3 metabolites while clozapine raised DOPA and HAV but not 3-MT. The importance of simultaneous determination of these 3 metabolites is discussed with relation to evaluation of the mechanism of action of these drugs and - more generally - of drugs acting on the dopaminergic system.

3,4-Dihydroxyphenylacetic Acid↗

A rapid and simple method for the determination of picogram levels of 3-methoxytyramine in brain tissue using liquid chromatography with electrochemical detection.

A rapid and simple technique using solvent extraction, ion-pairing extraction, and high pressure liquid chromatography with electrochemical detection has been developed for the determination of 3-methoxytyramine in striata of rats killed by microwave irradiation. The method is specific and reproducible (coefficient of variation among replications, +/- 4%); recovery of authentic 3-methoxytyramine added to the samples is 45-50%. 3-Methoxytyramine levels found with this technique in rat striata were 15 +/- 1.7 ng/g. The method has a sensitivity of about 0.2 pmol per brain sample. Monoamine oxidase inhibition with pargyline increased 3-methoxytyramine levels in rat striata, while catechol-O-methyltransferase inhibition with 3',4'-dihydroxy-2 methylpropiophenone completely depleted 3-methoxytyramine. The effects of nomifensine, quipazine, caroxazone, piribedil, and D-amphetamine were also examined. The 3-methoxytyramine concentrations in the brains of animals killed by decapitation or by microwave irradiation were compared.

Animals↗