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L de Angelis

Publications and source records attributed to L de Angelis.

At least 19 recordsLinked to original sources

Experimental anxiety and antiepileptics: the effects of valproate and vigabatrin in the mirrored chamber test.

The potential anxiolytic-like effects of valproate (VPA; 200, 300 and 400 mg/kg i.p.) and vigabatrin (GVG; 150, 300 and 450 mg/kg i.p.) were evaluated in an experimental model of anxiety in mice. The mirrored chamber test was the model selected. In this study, anxiogenic-like behavior was induced by pretreatment with m-chlorophenylpiperazine hydrochloride (m-CPP; 1 mg/kg i.p.). For comparative purposes, the effects of an established reference anxiolytic, lorazepam (LOR; 0.025, 0.05 and 0.10 mg/kg i.p.) were also evaluated. Results showed that 2 weeks of repeated treatment with 200, 300 and 400 mg/kg of VPA or, to a lesser extent, 300 and 450 mg/kg i.p. of GVG, antagonized the anxiogenic effects of m-CPP. VPA induced behavioral changes very similar to those produced by lorazepam, i.e., a decrease in the latency time to enter the mirrored chamber and an increase in the time spent in the mirrored chamber. The anxiolytic-like potency of GVG was lower than that of VPA in this test. In conclusion, these data provide additional evidence for the anxiolytic-like effects of VPA and substantiate its role in the treatment of anxiety disorders and in the withdrawal state of ethanol or sedative-hypnotics.

Animals↗

Ascorbic acid and atypical antipsychotic drugs: modulation of amineptine-induced behavior in mice.

To provide a detailed characterization of individual kinds of behavior produced by ascorbic acid in combination with typical (haloperidol) or atypical (clozapine, sulpiride and remoxipride) antipsychotic drugs, the 'open-field' test was selected. Amineptine, an indirect dopamine agonist, was used as an explicit model of dopaminergic activity. Results showed that amineptine (5-10-20 mg/kg i.p.), dose-dependently, increased ambulation and rearing. Ascorbic acid (62.5-125-250 mg/kg i.p.) markedly inhibited the behavior of mice as well as the amineptine-induced hyperactivity. A combination of each typical or atypical antipsychotic drug (except clozapine 2.5 mg/kg i.p.) with amineptine (20 mg/kg i.p.) induced a significant increase in ambulation and rearing over that seen with the antipsychotic drugs alone. The combination of antipsychotic drugs with ascorbic acid 250 mg/kg i.p. led to a decrease in open-field parameters when compared with controls. In conclusion, these data provide further in vivo support for the effect of ascorbic acid on dopaminergic system and demonstrate that the antidopaminergic effects of both typical and atypical antipsychotic drugs may be enhanced with concurrent administration of ascorbic acid.

Animals↗

The effects of ascorbic acid and oxiracetam on scopolamine-induced amnesia in a habituation test in aged mice.

The effects of a nootropic drug, oxiracetam (50-100-200 mg/kg ip), and a potent antioxidant agent, ascorbic acid (62.5-125-250 mg/kg ip), administered alone or in combination, were investigated on scopolamine-induced amnesia in a mouse habituation test. The light-dark aversion test was selected and was carried out in aged mice. Habituation to the test box occurred over a 3-day period, control mice showing a significant between-day increase in the time spent in the dark box, but not in the number of transitions. On Day 4, following post-trial administration over a 3-day period of oxiracetam (50-100 and 200 mg/kg ip) or ascorbic acid (62.5-125 and 250 mg/kg ip), a significant between-day increase in the time spent in the black area, but not in the number of transitions, was found. The combination of oxiracetam (100 mg/kg ip) with ascorbic acid (125 mg/kg ip) produced a similar pattern of results. The acute administration of scopolamine (0.25 mg/kg ip) to mice treated over a 3-day period with vehicle disrupted the habituation response. In mice that had received the 3-day treatment with oxiracetam or ascorbic acid or its combination, scopolamine failed to alter significantly the learning pattern. In conclusion, these data demonstrate that ascorbic acid, alone or in combination with oxiracetam, may prevent experimentally induced amnesia in aged mice.

Aging↗

Effects of valproate and lorazepam on experimental anxiety: tolerance, withdrawal, and role of clonidine.

The anxiolytic-like effects tolerance and withdrawal from chronic treatment with sodium valproate [200, 300, and 400 mg/kg, intraperitoneally (i.p.)] were compared with those of a known anxiolytic drug, lorazepam (0.025, 0.05, and 0.10 mg/kg, i.p.), in the light-dark aversion test in mice. Furthermore, we investigated whether acute treatment with clonidine, 0.03 mg/kg i.p., an alpha 2-adrenoceptor agonist, could reduce the increased anxiety on withdrawal from chronic treatment. Mice were given 14 daily i.p. injections of valproate, lorazepam, or vehicle and were tested in the light-dark aversion test 30 min or 24 or 48 h after the last drug or vehicle administration. Results showed that both acute and chronic valproate treatment reduced the aversion of mice for the light area, as well as increased the number of transitions, thus indicating an anxiolytic-like potential. Furthermore, in contrast to lorazepam, tolerance to the anxiolytic-like effects of valproate did not occur, and withdrawal from chronic treatment (300 mg/kg, i.p.) in our behavioral paradigm was not associated with any behavioral disturbances referring to an increased anxiety state. Finally, low doses of clonidine (0.03 mg/kg, i.p.) were shown to have anxiolytic properties and to reverse the anxiogenic effects of lorazepam on withdrawal.

Adrenergic alpha-Agonists↗

The anxiogenic-like effects of pentylenetetrazole in mice treated chronically with carbamazepine or valproate.

The chronic effects of carbamazepine administration (5, 10, 20 mg/kg i.p. daily for 14 days) on the anxiogenic response to pentylenetetrazole were studied in the light/dark aversion test. In mice, these effects were compared with those of sodium valproate (100, 200 and 300 mg/kg i.p.), a putative anxiolytic drug, and lorazepam (0.025, 0.05 and 0.10 mg/kg i.p.), a well-established anxiolytic drug. The results showed that the anxiogenic-like behavior induced by subconvulsant doses of pentylenetetrazole (15 mg/kg i.p.) was antagonized by the chronic administration of lorazepam as well as sodium valproate, a GABA agonist. In fact, the increased aversion of mice for the light compartment of the light/dark box was reduced. Carbamazepine failed to significantly alter the anxiogenic-like behavior of mice. These findings provide further evidence for the absence of anxiolytic properties of carbamazepine and for a behavioral anxiolytic profile of valproate similar to that of benzodiazepines.

Animals↗

Lithium treatment and the geriatric population.

The present review attempts to highlight selective concerns with regard to the use of lithium in the geriatric population. Several points as pharmacokinetics, prophylaxis, side-effects, intoxication deserve particular emphasis in relation to the elderly patient and are discussed. Furthermore, since the potential for drug interactions is greatly increased because of the greater number of drugs these patients take, the clinical significance of some drug interactions is also reported.

Aged↗

Behavioral effects of salbutamol and/or L-(+)-ascorbic acid in the mouse after single and multiple dosing.

The acute and chronic effects of salbutamol alone and L-(+)-ascorbic acid alone and in combination were evaluated on "open-field" test in mice. Administered singly and acutely (30 min before the test), both salbutamol (0.003 mmol/kg i.p.) and L-(+)-ascorbic acid (0.35-0.71 and 1.42 mmol/kg i.p.) significantly reduced ambulation scores. This decrease was higher in L-(+)-ascorbic acid - than in salbutamol-treated mice. Rearing behavior was significantly increased only in salbutamol-treated animals. In animals treated chronically (once a day for 15 days) the depression of salbutamol-induced ambulation was more marked than in mice treated acutely. This decrease was partially reversed by L-(+)-ascorbic acid treatment. With respect to rearing scores, a significant increase was found after salbutamol and L-(+)-ascorbic acid administered alone or in combination. In conclusion, these experiments show that salbutamol induces a direct effect on behavior, that is to reduce motor activity, being the reduction more marked after chronic treatment. The association of the beta 2-agonist with L-(+)-ascorbic acid can attenuate some of the depressant effects of chronic salbutamol administration on behavior.

Albuterol↗

Effects of caffeine and chlor-desmethyldiazepam on fighting behavior of mice with different reactivity baselines.

The effects of various doses of caffeine and of chlor-desmethyldiazepam on footshock-induced aggressive behavior were examined in mice with different baselines of aggressiveness. Caffeine significantly increased the number of fighting episodes with all the doses tested. This was more evident in mice with low rather than in those with high basal rates of agonistic response. Caffeine caused the appearance of minimal convulsive signs in mice subjected to a threshold electroshock which did not produce any seizure in the controls; it also increased metrazol toxicity. Chlor-desmethyldiazepam enhanced fighting behavior at doses of 0.04 and 0.08 mg/kg, but decreased it at 1.25 mg/kg. The first two doses produced the same effects as caffeine on electroshock test, but did not influence metrazol toxicity.

Aggression↗

Regional distribution of high affinity binding of 3H-adenosine in rat brain.

The high and low affinity adenosine binding sites with Kd values ranging respectively from 0.8 to 1.65 microM and from 3.1 to 13.86 microM were demonstrated in the following rat brain areas: cortex, hippocampus, striatum, cerebellum, diencephalon, and pons-medulla. Adenosine receptors involved in the high affinity binding seem to be mainly Ra-type. The analysis of the regional distribution of 3H-Adenosine showed the highest levels of specific binding in striatum and hippocampus; somewhat smaller values in cortex, cerebellum, and diencephalon, and even lower in pons-medulla.

Adenosine↗

Interaction of caffeine with benzodiazepines: behavioral effects in mice.

Three series of behavioral experiments, i.e. hole-board, open-field and spontaneous motor activity test, were carried out on mice with the goal of determining the effects of the interaction between caffeine and two peculiar benzodiazepines (BDZ). The drugs, desmethyldiazepam (DMDZ) and chlor-desmethyldiazepam (Cl-DMDZ), were administered acutely by the intraperitoneal route. In preliminary experiments, the effects of several doses of caffeine were examined in the three in order to obtain some indication of the doses to use for interaction experiments. Therefore, stimulant doses of caffeine (5, 10 and 20 mg/kg) were associated with the two benzodiazepines. It was found that BDZ counteracted the effect of caffeine in the hole-board and in the spontaneous motor activity tests. By contrast, in the open-field situation, the association always gave rise to an increase in exploration activity. Furthermore, the present investigations showed, once again, that chlor-desmethyldiazepam is more active than the other benzodiazepine.

Animals↗

Acute and chronic effects of three benzodiazepines in the social interaction anxiety test in mice.

The effects on active social interaction of acute and chronic dosage with diazepam (1 mg/kg), desmethyldiazepam (2 mg/kg), and chlor-desmethyl-diazepam (0.125 mg/kg) were studied in pairs of mice. The mice were tested under either high or low levels of illumination. In all cases acute drug treatment significantly reduced social interaction, but this was not seen with chronic treatment (9 days). Two of the drugs, diazepam and desmethyldiazepam, showed an anxiolytic action, i.e., these drugs resulted in significantly less variation in social interaction with the change in light levels, compared with vehicle-injected controls.

Animals↗

[Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)].

In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst.

Animals↗

Tissue distribution of 14C-heteronium bromide: radioactivity levels at different time intervals after oral administration in the rat.

The tissue distribution of radioactivity after oral administration to rats of 14C-heteronium bromide is measured by liquid scintillation counting and the results expressed as specific activity and percentage of administered radioactivity. From the data obtained in blood, liver, kidney. stomach, duodenum, cecum, large intestine and stool some conclusions can be drawn. Heteronium bromide undergoes a rapid systemic absorption, the radioactivity being present as early as 15 min from the administration, in all the tested organs. The blood levels show two peaks: one at 120 min and a second at 360 min. This diphasic behaviour can be explained either by the presence of an active enterohepatic circulation, as indirectly indicated by the data from liver and duodenum, or by a transient shift of the molecule from blood to other tissues, rich in polysulfuronic acids. The principal route of excretion is represented by the kidney, where consistent levels are reached at 120 min, while the intestinal route becomes evident at 240 min and reaches its maximum at 720 min. The complete metabolic cycle of the compound is long lasting, since in all the tested tissues, marked radioactivity levels are still present after 720 min. The pharmacokinetic profile obtained, suggesting a long persistence of the drug and/or of its metabolites in the organism, is in agreement with previous pharmacodynamic data showing a long lasting action for heteronium bromide.

Administration, Oral↗