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F Ponzio

Publications and source records attributed to F Ponzio.

At least 55 records · Page 3Linked to original sources

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↗

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↗

DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine)--a useful denervation tool for central and peripheral noradrenaline neurons.

The effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on monoamine neurons was studied in mice and rats. In mice DSP4 produced acutely a marked reduction of endogenous noradrenaline (NA), [3H]NA uptake and nerve density of the adrenergic nerves in the iris and atrium. Pronounced accumulations of NA were observed in non-terminal axons, which is a degenerative sign, while no changes were found in the NA cell bodies. A marked recovery of all parameters analysed was found as soon as 1 week after DSP4. In the mouse CNS, however, there was a marked and long-lasting NA reduction, especially in the cerebral and cerebellar cortex and spinal cord, leaving dopamine (DA) and serotonin (5-HT) neurons apparently unaffected. Administration of DSP4 to adult rats produced regional changes in the NA levels of the CNS were similar to those observed in the mouse. There were no indications of DSP4 affecting dopamine and adrenaline neurons in rat CNS, although a minor 5-HT depleting effect was noted. DSP4 treatment resulted in an increase in beta-adrenoceptor binding in vitro to homogenates from the cerebral cortex, using [3H]dihydroalprenolol as radioligand. Treatment of newborn rats with DSP4 caused permanent NA disappearance in the cerebral cortex and spinal cord, whereas marked NA increases were found in the pons-medulla and cerebellum. Administration of DSP4 to pregnant rats (gestation day 15) led to a marked and permanent NA depletion in the cerebral cortex and spinal cord in the offspring. The results support the view that DSP4 can produce an acute and relatively selective degeneration of NA nerve terminals in the rat and mouse. The results furthermore indicate that DSP4 (systemically administered) causes a preferential degeneration of NA nerve terminal projections originating from the locus coeruleus in the CNS. Since DSP4 can pass both the blood-brain and blood-placenta barrier and appears to have potent neurotoxic actions on NA neurons, DSP4 may serve as a useful denervation tool for the analysis of NA transmitter functions, particularly in the CNS of both adult and developing animals.

Amines↗

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↗

Noradrenaline and dopamine interaction in rat brain during development.

The effects of systemic treatment of newborn rats with the catecholamine neurotoxins 6-hydroxydopamine (6-OH-DA) or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the central dopamine (DA) and noradrenaline (NA) neurons were studied using neurochemical techniques. Both neurotoxins cause similar alterations of the postnatal development of the NA neurons with a pronounced NA denervation in the cerebral cortex and a NA hyperinnervation in the pons-medulla. The results did not show any neurotoxic action of neonatal 6-OH-DA or DSP4 treatment on the DA neurons. The tyrosine hydroxylase inhibition model was used to evaluate catecholamine turnover. The data showed a reduced DA turnover both in the cerebral cortex and striatum in young rats (12 days old) after neonatal 6-OH-DA or DSP4 treatment. After 6-OH-DA this effect could be blocked by pretreatment with the NA uptake blocker desipramine, which also prevented the 6-OH-DA induced alteration of the development of NA neurons. No clear-cut effect on DA turnover was seen in the adult stage after neonatal 6-OH-DA or DSP4, although a reduced DA turnover was observed in the cortex after an acute DSP4 treatment in adult rats. The results show that NA nerve terminals originating in the locus coeruleus NA neurons may be involved in regulating the functional activity of the DA nerve terminals both in the cerebral cortex and the striatum. This regulation appears to be facilitatory in nature and is present early in development.

Adrenergic Fibers↗

Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons.

The effect of various drugs was studied on 3-methoxytyramine (3-MT) concentrations in rat striatum. The drugs were chosen for their ability to interfere with the dopaminergic system at different levels. Dopamine (DA) acidic metabolites, i.e. homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were also measured. Changes of 3-MT, unlike those of DOPAC and HVA, seem to reflect the functional activity of dopaminergic neurons. In fact drugs believed to increase or decrease DA content in the synaptic cleft produce predictable changes of striatal 3-MT. Thus cocaine, nomifensine and d-amphetamine increase 3-MT concentrations while gamma-butyrolactone, alpha-methyltyrosine and apomorphine decrease it.

3,4-Dihydroxyphenylacetic Acid↗