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Biomedical subjects

F Fadda

Publications and source records attributed to F Fadda.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of spontaneous ingestion of ethanol on brain dopamine metabolism.

The effect of ethanol, either administered by gavage or voluntarily ingested, on brain dopamine (DA) metabolism was studied in alcohol-preferring and alcohol non-preferring rats. In alcohol non-preferring rats ethanol administration (2 g/kg) increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and reduced DA levels in the caudate nucleus and olfactory tubercle but was ineffective in the medial prefrontal cortex. In alcohol-preferring rats ethanol effect was greater than in non-preferring animals and ethanol influenced DA metabolism also in the medial prefrontal cortex. The effect of voluntary ethanol ingestion was studied in alcohol-preferring rats trained to consume their daily fluid intake within 2 hrs. Voluntary ingestion of ethanol (3.1 +/- 0.7 g/kg in 1 hr) increased DA metabolites and reduced DA levels in the caudate nucleus, olfactory tubercle and medial prefrontal cortex. The results suggest that voluntary ethanol ingestion increases the release of DA from nigro-striatal and meso-limbic DA neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats.

The ability of gamma-hydroxybutyric acid to suppress ethanol withdrawal syndrome was tested in male rats rendered physically dependent on ethanol by several intragastric administrations of ethanol (9-15 g/kg daily for 7 days). Gamma-hydroxybutyrate (0.25, 0.50 and 1.00 g/kg i.p.), administered 8 hr after the last ethanol dose, produced a dose-dependent inhibition of withdrawal signs such as tremors and audiogenically-induced seizures; the highest dose tested suppressed all ethanol withdrawal symptoms.

Animals↗
PubMed1987

Ethanol prevents stress-induced increase in cortical DOPAC: reversal by RO 15-4513.

Electric foot-shock increased DOPAC and decreased DA levels by about 70 and 20% respectively in the medial prefrontal cortex in rats. Pretreatment with diazepam (5 mg/kg IP) or ethanol (1.2 g/kg orally) prevented these stress-induced changes. The protective effect of diazepam and ethanol was eliminated by RO 15-4513 (5 mg/kg IP) a partial inverse benzodiazepine agonist.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Inhibition of voluntary ethanol intake in rats by a combination of dihydroergotoxine and thioridazine.

Dihydroergotoxine (DHET) decreased voluntary ethanol intake in rats selected for their stable ethanol preference (mean daily ethanol intake 8 g/kg). DHET inhibition was markedly potentiated by thioridazine. The potentiation is explained with a synergistic inhibitory effect on dopaminergic transmission: that is, DHET acting on dopamine (DA) autoreceptors and thioridazine preferentially inhibiting postsynaptic DA receptors.

Alcohol Drinking↗
PubMed1985

Suppression by progabide of ethanol withdrawal syndrome in rats.

Progabide, a specific and clinically used GABA receptor agonist, was tested for its ability to suppress ethanol withdrawal syndrome. Male rats were rendered physically dependent on ethanol by feeding for 12 days on a liquid diet in which ethanol isocalorically replaced dextrose. Progabide (100-400 mg/kg i.p.), administered 8 h after ethanol was withdrawn, produced a dose-related inhibition of both tremors and audiogenically induced seizures. A single dose of 400 mg/kg of progabide completely suppressed all ethanol withdrawal reactions. Seizures were more sensitive to the drug than tremors. The results support the view that a decrease in GABA transmission plays a role in ethanol withdrawal symptoms and suggest that progabide may be tested as a possible treatment of ethanol withdrawal syndrome in man.

Acoustic Stimulation↗
PubMed1984

Evidence for dopamine autoreceptors in mesocortical dopamine neurons.

The effect of different treatments which are thought to modify dopamine (DA) synthesis by an action on DA autoreceptors was compared in the caudate nucleus and two frontal cortical areas: the medial prefrontal cortex and dorsolateral frontal cortex, having the highest and lowest DA concentration, respectively, but having equal concentrations of norepinephrine (NE); the NE to DA ratio being 3:2 and 8:1, respectively. DA synthesis was measured by the rate of DOPA accumulation after inhibition of DOPA decarboxylase. Gamma-butyrolactone (GBL) (750 mg/kg) increased DOPA accumulation by 200% in the caudate nucleus but only by 40% in the medial prefrontal cortex and was ineffective in the dorsolateral frontal cortex. Apomorphine (25-100 micrograms/kg) decreased DOPA accumulation by 7-30% in the medial prefrontal cortex and by 20-40% in the caudate nucleus in a dose-dependent manner. N-n-propylnorapomorphine (NPA) produced a similar effect within the dose range of 2.5-10 micrograms/kg. Both DA agonists were completely ineffective in the dorsolateral frontal cortical area. Haloperidol (0.5 mg/kg) increased DOPA accumulation by 80 and 220% in the medial prefrontal cortex and the caudate nucleus, respectively. It is concluded that DA autoreceptors regulate DA synthesis in the medial prefrontal cortex as in the caudate nucleus. Moreover, it was found that DOPA accumulation was approximately equal in the medial prefrontal cortex, with dense dopaminergic innervation, as in the dorsolateral area, devoid of dopaminergic terminals, suggesting that only a small fraction of cortical DA synthesis takes place in dopaminergic neurons, while the major part occurs in noradrenergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Butyrolactone↗
PubMed1984

Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats.

In unanesthetized paralyzed rats, i.v. ethanol administration (0.5-2.0 g/kg) increased (by 30-120%) the firing rate of dopaminergic (DA) neurons in the substantia nigra, pars compacta. Doses of 4.0 g/kg or higher produced an initial stimulation followed by a long-lasting inhibition of firing. On the contrary, in rats anesthetized with halothane (2.5% v/v in air) or with chloral hydrate (400 mg/kg), doses of ethanol up to 2 g/kg failed to activate DA neurons, while a dose of 4 g/kg inhibited neuronal firing without the initial stimulant response. In unanesthetized-curarized rats, the i.v. administration of either chloral hydrate (100-400 mg/kg) or pentobarbital (10-40 mg/kg) or the inhalation of halothane (0.5-2.5% v/v in air) produced a dose-dependent increase in the firing rate of DA neurons. However, the maximum increase produced by these anesthetics was less pronounced and shorter lasting than that produced by ethanol.

Action Potentials↗
PubMed1983

Suppression of voluntary ethanol consumption in rats by gamma-butyrolactone.

The effect of gamma-butyrolactone (GBL) on voluntary ethanol intake was studied in a group of Wistar rats in which a stable preference had been induced by exposure to increasing ethanol concentrations. These rats drank 60% of their daily fluid intake as 15% ethanol solution, corresponding to about 6 g ethanol/kg/day. GBL, injected intraperitoneally at the dose of 200 mg/kg, twice daily for 3 consecutive days, decreased ethanol intake by about 80% on the days of treatment, but did not reduce total fluid intake. Ethanol intake remained significantly reduced up to the 5th day following cessation of GBL administration. GBL, up to a concentration of 10(-3) M, inhibited neither alcohol-dehydrogenase nor aldehyde-dehydrogenase in rat liver homogenates, nor dopamine-beta-hydroxylase in homogenates of adrenal medulla or hypothalamus of rats. It is suggested that inhibition of firing in dopaminergic neurons mediates the suppressant effect of GBL on ethanol preference.

4-Butyrolactone↗
PubMed1982

Delayed inhibition of dopamine synthesis by gamma-butyrolactone and baclofen: dopamine autoreceptor supersensitivity?

The administration of gamma-butyrolactone (GBL) (750 mg . kg-1 i.p.) and baclofen (20 mg . kg-1 i.p.) to rats caused a transient increase followed by a long-lasting decrease in striatal dopamine (DA) synthesis, as measured by DOPA accumulation after decarboxylase inhibition. DA synthesis was reduced to 40-50% of the control value for 2-12 h following either treatment. The GBL- and baclofen-induced inhibition of DN synthesis was reversed by haloperidol (2-5 mg . kg-1 i.p.) and by a second dose of baclofen or GBL. The subcutaneous dose of 15 mg . kg-1 of apomorphine, insufficient to decrease DA synthesis in control rats, produced a further decrease in DA synthesis in animals pretreated with baclofen. These results suggest that the delayed DA synthesis inhibition following GBL or baclofen treatment was due to stimulation of supersensitive DA autoreceptors.

4-Butyrolactone↗
PubMed1982

Evidence for dopamine autoreceptors controlling dopamine synthesis in the substantia nigra.

The effect of apomorphine and haloperidol on DOPA accumulation after inhibition of DOPA decarboxylase activity with NSD 1015 was compared in the substantia nigra (SN) and caudate nucleus (CN) of normal rats and rats deprived of nigral afferences from the striatum by means of intrastriatal kainic acid. In normal rats apomorphine decreased DOPA accumulation to the same extent in both the SN and CN. However, haloperidol produced a more pronounced increase in DOPA accumulation in the CN than in the SN. The effect of both drugs still persisted in the SN and CN after destruction of the neuronal strionigral feedback loop with kainic acid. The results provide evidence for the existence of nigral dopamine autoreceptors controlling dopamine synthesis in the SN.

Animals↗
PubMed1982

N-n-propyl-norapomorphine: an extremely potent stimulant of dopamine autoreceptors.

N-n-propyl-norapomorphine (NPA) is 10-20 times more potent than apomorphine in producing hypomotility and inhibiting both striatal and limbic dopamine (DA) synthesis and the firing rate of nigral dopaminergic cells in rats. The threshold subcutaneous doses of NPA and apomorphine to significantly inhibit motor activity or DA synthesis are 1.25 and 24 microgram/kg, respectively. The intravenous ED 50 of NPA to inhibit dopaminergic firing is 0.36 microgram/kg and that for apomorphine is 9.1 microgram/kg. The above effects of NPA, as those of apomorphine, are antagonized by haloperidol and, stereospecifically by (--) sulpiride.

Animals↗
PubMed1982

Effect of dopamine agonists and antagonists on DOPA formation in the substantia nigra.

The effect of different psychotropic drugs on the rate of DOPA accumulation after administration of a decarboxylase inhibitor (NSD 1015) was compared in the substantia nigra (SN) and caudate nucleus (CN) by a new radioenzymatic method. Inhibition of monoamine oxidase with pargyline or stimulation of dopamine (DA) receptors with apomorphine, N-n-propylnorapomorphine or D-amphetamine reduced DOPA formation in the CN and SN to the same extent. Vice versa, both inhibition of DA receptors with haloperidol or (-)sulpiride and depletion of DA concentration with reserpine enhanced DOPA formation to a greater extent in the CN than in the SN. Apomorphine antagonized not only the effect of haloperidol and (-)sulpiride, but also, and even more effectively, that of reserpine. The results indicate that DA synthesis in the SN is controlled by both end-product inhibition and DA receptor-mediated mechanisms.

Animals↗
PubMed1981

Effect of stress and ACTH on dopamine metabolism in the nucleus accumbens and frontal cortex.

The effect of ACTH and electric foot shock stress on DOPAC content were determined in the frontal cortex and nucleus accumbens. Twenty min of stress enhanced DOPAC levels in the frontal cortex and in the nucleus accumbens by about 80% and 35%, respectively. On the other hand, a single dose of ACTH failed to change DOPAC concentration in the above brain areas. The present results show that the activation of mesolimbic and mesocortical dopaminergic systems is not mediated by ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1981

Repeated electroconvulsive shock prevents the sedative effect of small doses of apomorphine.

Repeated electroconvulsive shock (ECS) (one shock daily for 8 days), but not single ECS, eliminates the sedative response to small doses of apomorphine (25--1000 microgram/kg) and potentiates the stimulant response to high doses (200 microgram/kg) of the drug in rats. This effect is observed 1 and 4 days after the last ECS. However, repeated ECS does not prevent the inhibitory effect of apomorphine on dopamine (DA) synthesis. The results suggest that repeated ECS may lead to the development of subsensitivity in DA receptors that mediate sedation and that these receptors are differentiated from those controlling DA synthesis.

Animals↗
PubMed1980

Effect of acute and chronic ethanol on dopamine synthesis in the caudate nucleus, substantia nigra and frontal cortex.

A single oral administration of 3.2 g/kg ethanol to normal rats increased 3,4-dihydroxyphenylacetic acid (DOPAC) content and DOPA formation in the caudate nucleus but had no effect in frontal cortex and substantia nigra and did not modify dopamine (DA) levels in any of the brain regions analyzed. Complete tolerance to the stimulant effect on DOPA formation developed after chronic ethanol-treatment (3.2 g/kg daily for 60 days). However ethanol administration to ethanol dependent rats produces a marked DA depletion and increases DOPAC concentration in the brain areas studied. The present results show that acute and chronic ethanol release DA stores, but only in the acute conditions DA depletion is compensated by enhanced synthesis.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Effect of ethanol on the metabolism of regional brain dopamine.

Acute oral administration of ethanol (3.2g/kg) to rats increased (DOPAC) levels in the caudate nucleus, but had no effect on DOPAC levels in the substantia nigra and frontal cortex and failed to modify dopamine content in any of the above areas. On the other hand, the administration of the same dose of ethanol to rats which had been chronically treated with ethanol (3.2g/kg daily for 60 days), produced a decrease of DA content and a parallel increase of DOPAC levels in all areas studied. In chronically treated rats, 24 hrs after last ethanol administration dopamine levels in the frontal cortex were 60% higher than in controls. The results suggest that ethanol administration causes dopamine release in different brain areas.

3,4-Dihydroxyphenylacetic Acid↗