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F Fadda

Publications and source records attributed to F Fadda.

At least 37 records · Page 2Linked to original sources
PubMed1995

Blockade of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS-382.

The present study was designed to assess the ability of the newly synthetized, selective gamma-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700 mg/kg GHB and the right arm after water. Once discrimination was acquired, combination of different doses of NCS-382 (0, 12.5, 25.0 and 50.0 mg/kg, IP) and GHB training doses were tested for blockade of GHB discrimination. NCS-382 dose-dependently blocked GHB-appropriate responding in both the 300 and 700 mg/kg GHB rat groups. The results of the present study indicate that the discriminative stimulus properties of GHB are mediated via stimulation of GHB receptors.

Animals↗
PubMed1995

Effects of the calcium channel antagonist darodipine on ethanol withdrawal in rats.

The effect of the dihydropyridine calcium channel antagonist, darodipine, on ethanol withdrawal syndrome was examined in rats made dependent on ethanol by repeated ethanol administration for six consecutive days. Chronic co-administration of darodipine prevented the severity of ethanol withdrawal signs in a dose-dependent fashion. By contrast, acute administration of darodipine during the ethanol withdrawal phase was ineffective in reversing the withdrawal symptoms. The results suggest that the presence of darodipine in the central nervous system during the adaptative responses to ethanol is necessary to reduce the severity of the withdrawal syndrome. They also provide further evidence for a potential clinical usefulness of dihydropyridine calcium channel blockers in treatment of ethanol withdrawal.

Animals↗
PubMed1994

Blockade of ethanol discrimination by isradipine.

The effect of the dihydropyridine Ca2+ channel antagonist, isradipine, on ethanol discrimination was assessed in rats trained to discriminate 1.5 g/kg ethanol from water in a T-maze, food-reinforced drug discrimination procedure. Pretreatment with isradipine (0, 1.0, 3.0 and 5.0 mg/kg i.p.) resulted in a dose-dependent blockade of ethanol discrimination. The results of the present study suggest that L-type Ca2+ channels are involved in the mediation of ethanol discriminative stimulus effects.

Animals↗
PubMed1992

gamma-Hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study.

The effect of gamma-hydroxybutyric acid on alcohol consumption and alcohol craving in alcoholics was investigated in a randomized double-blind study versus placebo. Patients were treated as outpatients during a three month period either with gamma-hydroxybutyric acid (50 mg/kg/day, divided into three daily doses) or with placebo. Of the 82 alcoholics that entered the study, 71 completed it, 36 in the gamma-hydroxybutyric acid and 35 in the placebo group. Alcohol consumption was assessed by the subject's self report. At the 3rd month of treatment, 11 patients in the gamma-hydroxybutyric acid group referred to be abstinent and 15 referred controlled drinking; while in the placebo group only two and six patients referred abstinence and controlled drinking, respectively. Serum-gammaglutamyl-transferase activity correlated with the admitted alcohol consumption. Gamma-hydroxybutyric acid treatment decreased alcohol craving during the 3 months of treatment. Transient side effects were noted by six patients on gamma-hydroxybutyric acid and two on placebo. The results suggest that gamma-hydroxybutyric acid may be useful in the treatment of alcohol dependence.

Adult↗
PubMed1992

Isradipine and other calcium channel antagonists attenuate ethanol consumption in ethanol-preferring rats.

The present work is concerned with studying of the ability of different calcium channel antagonists to modify voluntary ethanol ingestion by rats selectively bred for high ethanol preference. The compounds were given s.c. thrice daily for 5 days at doses that did not produce locomotor impairment. While nifedipine, darodipine, and verapamil (each at the dose of 20 mg/kg thrice daily) produced a modest reduction in ethanol intake, isradipine (at the dose of 1 mg/kg three times a day) reduced ethanol intake by over 70%. For all compounds, the reduction in ethanol intake was compensated by a proportional increase in water consumption and the inhibitory effect persisted throughout the 5 days of treatment. The data indicate that calcium channel antagonists exhibit quite different potency in reducing ethanol preference, however this action is a general property of this class of compounds.

Alcohol Drinking↗
PubMed1992

Alcohol-preferring rats have fewer dopamine D2 receptors in the limbic system.

Dopamine D2 receptors in nucleus accumbens, olfactory tubercle and caudate nucleus of Sardinian ethanol-preferring (SP), and non-preferring (SNP) rats were compared by using [3H]YM-09151-2 binding. SP rats exhibited, in each area, lower density of D2 receptors than SNP and unselected Wistar (UW) rats. The results suggest that reduction in D2 receptors in SP rats may be relevant to their innate preference for alcohol.

Alcohol Drinking↗
PubMed1992

Metadoxine (pyrrolidone carboxylate of pyridoxine) antagonizes the locomotor-stimulatory effect of ethanol in mice.

The effects of metadoxine (pyrrolidone-carboxylic acid; PCA) and pyridoxine on the locomotor responses to ethanol in mice were compared. Metadoxine (200 and 400 mg/kg i.p.) and PCA (86 and 172 mg/kg) prevented, in a dose-related manner, the locomotor stimulant effect of a low dose of ethanol (1.5 g/kg i.p.), whereas pyridoxine (228 mg/kg i.p.) was completely ineffective. Neither compound modified the sedative effect of a high ethanol dose (2.5 g/kg i.p.). The results indicate that the antagonistic effect of metadoxine on ethanol stimulant response is due to the PCA component of the molecule.

Animals↗
PubMed1991

Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats.

In unanesthetized rats the intravenous (i.v.) administration of gamma-hydroxybutyric acid (GHB) at the doses of 50-400 mg/kg produced a dose-related stimulation (10-56%) of the firing rate of dopaminergic (DA) neurons in the pars compacta of the substantia nigra. Doses of 1000 and 1500 mg/kg inhibited the firing rate almost completely. In unanesthetized rats the intraperitoneal injection of GHB at the dose of 750 mg/kg produced a brief initial stimulation (23%) followed by a modest reduction in the firing rate (29%). On the other hand, in chloral hydrate-anesthetized rats the i.v. administration of GHB at cumulative doses of up to 200 mg/kg failed to modify the firing rate of DA neurons, while a cumulative dose of 400 mg/kg suppressed neuronal firing. The results indicate that sub-anesthetic doses of GHB stimulate the firing rate of DA neurons in unanesthetized rats.

Anesthesia, General↗
PubMed1991

MDL 72222, a selective 5-HT3 receptor antagonist, suppresses voluntary ethanol consumption in alcohol-preferring rats.

The effect of the selective 5-HT3 receptor antagonist MDL 72222 on voluntary ethanol consumption was examined in Sardinian ethanol-preferring (SP) rats in a free choice (10% ethanol and water) experiment. SP rats consumed 8.1 +/- 1.1 g/kg ethanol daily. MDL 72222 treatment (3.0, 5.0 and 7.0 mg/kg i.p. 3 times daily for 6 days) inhibited ethanol consumption during the 6 days of treatment by 25%, 50% and 75%, respectively, without modifying total fluid intake. We suggest that 5-HT3 receptor activation plays a permissive role in alcohol preference.

Alcohol Drinking↗
PubMed1991

Genetic sensitivity to effect of ethanol on dopaminergic system in alcohol preferring rats.

The effect of ethanol (etOH) on dopamine (DA) metabolism in the caudate nucleus (CN), olfactory tubercle (OT) and medial prefrontal cortex (MPFC) was compared in 2 selectively bred lines of rats, one etOH-preferring (sP) and the other -non preferring (sNP). EtOH (2 g/kg per os), administered 60 min before killing, caused a significant increase in concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and reduced DA levels in CN and OT in sNP rats. On the other hand in sP rats, etOH increased the content of DA metabolites in all the 3 areas analyzed. These changes induced by etOH in DA metabolism were significantly greater in sP than in sNP rats. The above data indicate that sP rats have a genetic high sensitivity to etOH effect on DA metabolism probably linked to etOH preference.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Alcohol-preferring rats: genetic sensitivity to alcohol-induced stimulation of dopamine metabolism.

The effect of ethanol on brain dopamine (DA) metabolism in the caudate nucleus (CN), olfactory tubercle (OT) and medial prefrontal cortex (MPFC) was compared in two selectively bred rat lines, one ethanol preferring and the other ethanol nonpreferring. Male rats from the 16th and 17th generations of both lines that never experienced ethanol beforehand were used. No differences in the basal concentrations of DA and its metabolites, DOPAC and HVA, in the above brain regions were found between the two lines. The oral administration of 2 g/kg of ethanol to ethanolnonpreferring rats increased DOPAC and HVA and reduced DA levels in the CN and OT but was ineffective in the MPFC. On the other hand, ethanol administration to ethanol-preferring rats decreased DA content and increased DOPAC and HVA levels, not only in the CN and OT, but also in the MPFC. Moreover, the changes induced by ethanol on DA metabolism in the latter group were significantly greater than in ethanol nonpreferring rats. These results indicate that ethanol preferring rats have a genetic high sensitivity to the ethanol effect on DA metabolism, and suggest that such a trait might play a role in ethanol preference.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Ro 19-4603, a benzodiazepine receptor inverse agonist, attenuates voluntary ethanol consumption in rats selectively bred for high ethanol preference.

The effect of Ro 19-4603, a novel potent partial inverse agonist of benzodiazepine (BZ) receptors, on voluntary ethanol intake was examined in a rat line selectively bred for ethanol preference (Sardinian ethanol preferring, sP, rats). Ro 19-4603, 1 mg/kg i.p., three times daily, reduced voluntary ethanol consumption by about 40% during 7 days of treatment, but failed to reduce water intake. The results suggest that the GABA/BZ receptor complex may play a role in the reinforcing property of ethanol.

Alcohol Drinking↗
PubMed1990

[Experimental models of alcoholism].

Ethanol causes behavioral effects in rats and mice similar to those observed in humans. Moreover, by selective breeding, lines of rats or mice have been obtained that prefer ethanol solution to water and vice versa (ethanol-preferring and ethanol-avoiding animals). Recent studies suggest that ethanol stimulates GABA receptor-mediated opening of the chloride channels in neuronal membranes, and that some behavioral responses to ethanol, such as its sedative and anxiolytic effects, are mediated by central GABA receptors. Recently, we have shown that ethanol suppresses the firing of neurons in the pars reticulata of the substantia nigra, which exert an inhibitory control over dopaminergic neurons. Escaping from inhibitory control, the latter neurons are stimulated by ethanol. Dopaminergic neurons especially sensitive to ethanol are those of the meso-cortico-limbic system, belonging to the "pleasure centers" of the brain. In addiction, it has been shown that ethanol stimulates dopamine metabolism in different brain areas, but more effectively so in ethanol-preferring than in ethanol-avoiding rats. Finally, voluntary ethanol intake modifies dopamine metabolism in different brain areas.

Alcoholism↗
PubMed1990

Voluntary alcohol drinking increases brain dopamine metabolism in rats.

The effect of ethanol on dopamine (DA) metabolism in two selectively bred lines of rats, one alcohol-preferring (sP) and the other--non-preferring (sNP), was studied. Ethanol administration (2 g/kg per os) produced in the two lines of rats a decrease of DA content and an increased concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the caudate nucleus, olfactory tubercle and medial prefrontal cortex in both lines, but the effect was significantly greater in sP than in sNP rats. Moreover, in sP rats, the voluntary consumption of ethanol increased DOPAC and HVA levels in the above areas. In these animals, DOPAC and HVA accumulation was associated with a small depletion in DA content, suggesting that ethanol releases DA from stores.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome.

The effect of gamma-hydroxybutyric acid (GHB) on ethanol withdrawal syndrome in alcoholics was investigated in a randomised double-blind study. Patients with withdrawal symptoms were treated either with GHB (orally in a syrup preparation) (11 patients) or with the syrup alone (12). GHB treatment (50 mg/kg) led to a prompt reduction in withdrawal symptoms, such as tremors, sweating, nausea, depression, anxiety, and restlessness. The only side-effect was dizziness. GHB may be useful in the management of alcohol withdrawal syndrome in man.

Administration, Oral↗
PubMed1989

Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain.

The effect of two calcium antagonists, nimodipine and flunarizine, on striatal dopamine (DA) metabolism in rats was compared. Flunarizine (5-20 mg/kg i.p.) caused a dose-dependent increase in the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Following the 20 mg/kg dose, DOPAC levels were maximally elevated by about 50% from 2 to 12 hrs after treatment. On the contrary, nimodipine at the dose of 20 mg/kg i.p. produced a modest decrease in DOPAC levels. Neither calcium antagonist modified DA content. However, both nimodipine and flunarizine, at the dose of 20 mg/kg, markedly reduced the accumulation of DOPAC in the caudate nucleus induced by haloperidol (1 mg/kg). It is suggested that flunarizine, but not nimodipine, has a neuroleptic-like action, whereas the two calcium antagonists have in common the ability to attenuate the hyperactivity of DA neurons.

3,4-Dihydroxyphenylacetic Acid↗
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↗