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Biomedical subjects

M Sansone

Publications and source records attributed to M Sansone.

At least 55 records · Page 3Linked to original sources

The role of trazodone metabolism in its inhibitory action on avoidance response.

To assess the role of trazodone metabolism in its depressant action on conditioned avoidance response we investigated whether in the mouse brain 3-chlorophenylpiperazine (CPP) is formed from trazodone, whether trazodone metabolism is affected by a drug metabolism inhibitor, proadifen, and how trazodone, CPP and their combinations act on avoidance responses in proadifen-pretreated mice. It was found that CPP is formed from trazodone in mice, that proadifen inhibits trazodone metabolism, and that the moderate and transient inhibitory effect of trazodone on avoidance responses is dramatically potentiated and prolonged in proadifen-pretreated mice. This effect, and inhibition of unconditioned escape response observed in mice receiving lower doses of trazodone after proadifen pretreatment, were counteracted by CPP. The results indicate that the inhibitory action of trazodone on avoidance response is caused by the parent compound, and that it is brief and moderate because of the rapid metabolism of the drug with formation of CPP which counteracts the depressant effect of the parent compound.

Animals↗

Prolongation of thiopentone-induced sleep by trazodone and its metabolite, m-chlorophenylpiperazine.

Trazodone and its metabolite, m-chlorophenylpiperazine (CPP) prolonged significantly thiopentone-induced sleep in mice. Neither trazodone, nor CPP changed the cerebral concentrations of thiopentone. As cyproheptadine by itself did not affect thiopentone sleep and did not antagonize the effect of CPP, the effect of trazodone and CPP seems to be independent of their respective 5-HT-antagonistic and 5-HT-agonistic properties.

Anesthesia↗

Improvement of avoidance acquisition by the nootropic drug oxiracetam in mice.

The nootropic drug, oxiracetam (25 or 50 mg/kg i.p.), was tested in two inbred strains of mice, subjected to shuttle-box avoidance training. The drug improved avoidance acquisition in good performers BALB/c mice more than in poor performers C57BL/6 mice. In both cases the avoidance facilitating action was evident only if training was preceded by a five-day pretreatment. The nootropic prototype, piracetam (100 mg/kg), facilitated avoidance acquisition in pretreated BALB/c, but not in C57BL/6 mice.

Animals↗

Interaction between nootropic drugs and methamphetamine on avoidance acquisition but not on locomotor activity in mice.

Two nootropic drugs, oxiracetam and piracetam, were tested, alone or in combination with methamphetamine, on locomotor activity and shuttle-box avoidance acquisition in mice of the C57BL/6 strain. Oxiracetam (50 mg/kg/day) and piracetam (100 mg/kg/day) had no effect when given alone, but significantly increased avoidance responses when combined with methamphetamine (0.5, 1 and 2 mg/kg). On the contrary, the two nootropic agents did not affect locomotor stimulation induced by methamphetamine. The results suggest that nootropic drugs may interact with methamphetamine in behavioural tests in which learning and memory processes are involved.

Animals↗

Opposite action of m-chlorophenylpiperazine on avoidance depression induced by trazodone and pimozide in CD-1 mice.

m-Chlorophenylpiperazine (CPP) given in doses up to 2 mg/kg did not affect conditioned avoidance responses (CAR) of CD-1 mice pre-trained in a shuttle box. It reversed the inhibitory action of trazodone (10 mg/kg) on CAR, but dose-dependently potentiated the inhibitory effect of pimozide (0.2 and 0.5 mg/kg). Apparently, dopaminergic transmission is important for the attenuating effect of CPP on CAR inhibition.

Animals↗

Locomotor depression by the opioid benzodiazepine tifluadom in mice.

Several doses of tifluadom, an opioid benzodiazepine with affinity for opioid kappa receptors, were tested on analgesia and locomotor activity in two strains of mice, the C57BL/6 and the DBA/2. The analgesic properties of the compound were confirmed in both strains by a tail flick test. As concerns locomotor activity both strains, that in previous researches showed opposite responses to opiates, were depressed by tifluadom, suggesting the involvement of kappa receptors in this effect.

Analgesia↗

Opposite effects of chlordiazepoxide and serotonin receptor antagonists on morphine-induced locomotor stimulation in mice.

Chlordiazepoxide and two serotonin receptor antagonists showed opposite effects when tested for their influence on morphine-induced locomotor stimulation in mice. Chlordiazepoxide enhanced morphine-induced hyperactivity, which was antagonized by cyproheptadine and mianserin. The results indicate that the enhancement of morphine-induced locomotor stimulation is not attributable to an antiserotonergic action of the benzodiazepine compound.

Animals↗

Different effects of 3-chlorophenylpiperazine on locomotor activity and acquisition of conditioned avoidance response in different strains of mice.

Mice of C57BL/6 (C57), Balb/c (BALB), and CD-1 (CD) strains were injected with 3-chlorophenylpiperazine (CPP), 1-10 mg/kg ip, and their exploratory and basal locomotor activities and acquisition of conditioned avoidance response in a shuttle-box were tested. In C57 mice CPP did not affect either locomotor activity or shuttle-box performance. In BALB mice CPP inhibited both basal and exploratory activities (the latter only in higher doses) and facilitated the acquisition of conditioned avoidance response. In CD mice CPP did not affect exploration, but inhibited basal locomotor activity and facilitated the shuttle-box performance. It is concluded that there exist large interstrain differences in responsiveness of mice to CPP, and that the drug may facilitate acquisition of conditioned avoidance response through a strain-specific, serotonin-independent mechanism.

Animals↗

Dopamine receptors in the striatum and limbic system of various strains of mice: relation to differences in responses to apomorphine.

Dopamine receptors, defined as [3H]spiroperidol binding sites, had similar population parameters in the limbic forebrain of C57BL/6, Albino Swiss and DBA/2 mice, but the parameters of the striatal populations were different: not only the densities differed among themselves, but the KD value of the striatal dopamine receptors of DBA/2 mice was significantly higher than that in the two remaining strains. Behavioral responses of Albino Swiss mice to apomorphine: biphasic effect of apomorphine on locomotor activity and stereotypy characterized by high motility, frequent rearing and sharp, not very frequent bites, were similar to those described earlier for C57BL/6 mice, and differed from those reported for DBA/2 mice. The results suggest that the difference in responding to apomorphine in various strains of mice may be related to differences in their striatal dopamine receptors.

Animals↗

Analysis of the difference in the behavioral effects of apomorphine in C57BL/6 and DBA/2 mice.

The influence of pimozide on the effects of apomorphine on locomotor activity and stereotypy was studied in two inbred strains of mice. In C57BL/6 mice, in which apomorphine did not produce stereotypy of gnawing, the biphasic effect of apomorphine on locomotor activity (hypomotility followed by hypermotility) was unaffected by pimozide. In DBA/2 mice, in which high doses of apomorphine produce hypomotility and compulsive gnawing, both these effects (but not hypomotility produced by low doses of apomorphine) were counteracted by pimozide. The results are consistent with the assumption that both strains of mice have separate inhibitory and stimulatory dopamine receptors mediating locomotor activity. In addition, DBA/2 but not C57BL/6 mice have dopamine receptors which mediate stereotypy and are sensitive to pimozide.

Animals↗

Avoidance facilitation by chlordiazepoxide-amphetamine combinations in mice: effect of alpha-methyl-p-tyrosine.

Chlordiazepoxide (CDP) and amphetamine (AMPH) were tested, alone or in combination, in BALB/c mice pretreated with alpha-methyl-p-tyrosine (AMT) and subjected to shuttle-box avoidance training. CDP and AMPH, given alone, partly reversed avoidance depression induced by 50 mg/kg of AMT, but were ineffective in mice pretreated with 100 mg/kg of AMT. Stronger effects were produced by CDP-AMPH combinations, which also improved avoidance performance in mice pretreated with the higher dose of AMT. The results suggest that catecholamines may play a role in the facilitation of avoidance induced by CDP, especially when given in combination with AMPH.

Amphetamine↗

Influence of benzodiazepine tranquilizers on scopolamine-induced locomotor stimulation in mice.

Four benzodiazepine tranquilizers have been tested, alone or in combination with scopolamine, on the spontaneous locomotor activity of BALB/c mice. Scopolamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. These effects are similar to those exerted by the four benzodiazepines on amphetamine-induced locomotor stimulation and allow the same differentiation between the four derivatives.

Animals↗