Biomedical subjects

M Sansone

Publications and source records attributed to M Sansone.

At least 19 recordsLinked to original sources

PubMed1999

Attenuation by nimodipine of amitriptyline-induced avoidance impairment in mice.

The effects of the dihydropyridine calcium channel blocker nimodipine on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box training and in previously trained mice of the DBA/2 strain. Nimodipine (0, 0.5, 1, 2.5, or 5 mg/kg) had no effect alone, but attenuated the avoidance impairment induced by 5 mg/kg amitriptyline on avoidance acquisition, as well as on a previously learned avoidance response. The avoidance improving action of the calcium channel blocker was less evident in mice receiving a larger dose (7.5 mg/kg) of the antidepressant drug. The effect of nimodipine did not appear to be specifically related to the avoidance impairment induced by amitriptyline, because the calcium antagonist also attenuated the avoidance impairing action of the neuroleptic chlorpromazine. The avoidance impairment induced by amitriptyline and chlorpromazine, and the related ameliorating action of nimodipine, seem imputable to drug effects on the performance of the avoidance response, rather than to interferences with learning processes. The results suggest that, in the case of concomitant administration, nimodipine could alleviate adverse side effects of tricyclic antidepressant, i.e., psychomotor disturbances.

Amitriptyline↗

PubMed1998

Shuttle-box avoidance learning in mice: improvement by combined glucose and tacrine.

Glucose and the acetylcholinesterase inhibitor tacrine were tested, alone and in combination, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose alone (50-400 mg/kg) had no significant effect, while tacrine alone (0.5-3 mg/kg) improved avoidance acquisition at the dose of 2 mg/kg only. Significant avoidance learning improvements were instead produced by 50 or 100 mg/kg glucose combined with 0.5 or 1 mg/kg tacrine. The effects on shuttle-box avoidance acquisition produced by glucose combined with a cholinomimetic agent support the hypothesis that cholinergic mechanisms may be involved in the action of glucose on learning and memory. However, the main finding of the present study is related to the enhancement by glucose of the learning improving action of a drug clinically used as cognitive enhancer.

Animals↗

PubMed1997

Nimodipine on shuttle-box avoidance learning in mice: no impairment but slight improvement.

The dihydropyridine calcium channel antagonist nimodipine was tested in mice of CD-1, C57BL/6, and DBA/2 strains subjected to shuttle-box avoidance training. In contrast with some findings of other authors showing impairment of shuttle-box avoidance learning by low doses of the drug in rats, nimodipine given IP before each training session at doses of 0.25, 0.5, 1, 2.5, or 5 mg/kg never impaired avoidance acquisition in mice. On the contrary, one dose of nimodipine (1 mg/kg) significantly improved avoidance acquisition in mice of the DBA/2 strain. The drug failed to impair avoidance performance in DBA/2 mice even if given acutely in the middle (third session) or at the end (fifth session) of the training period. The results contradict studies showing cognitive impairment induced by calcium channel blockers, and may provide some limited evidence in support of improved cognitive function in normal animals, although this effect is much less evident than in aged or brain-damaged subjects.

Animals↗

PubMed1997

Prevention of amitriptyline-induced avoidance impairment by tacrine in mice.

The effects of two cognition enhancers on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box avoidance acquisition and in previously trained mice of the DBA/2 strain. The nootropic agent piracetam (50, 100 or 200 mg/kg, i.p.) had slight or no effect in mice receiving amitriptyline (5 or 10 mg/kg, i.p.). Conversely, the acetylcholinesterase inhibitor tacrine (0.5, 1, 2 or 3 mg/kg, i.p.) prevented the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response. The avoidance disrupting action produced by 10 mg/kg of the antidepressant drug was not affected by the anticholinesterase drug. The preventing action of tacrine seems specifically related to the avoidance impairment induced by amitriptyline, since the acetylcholinesterase inhibitor did not reduce, but enhanced the avoidance impairing action of the neuroleptic chlorpromazine. Taken together, the results indicate that amitriptyline-induced avoidance impairment, and the related preventing action of tacrine, may be ascribed to drug effects on the performance of the avoidance response, rather than to interferences with learning processes.

Amitriptyline↗

PubMed1996

Effects of low doses of physostigmine on avoidance learning and EEG in two strains of mice.

The effects of the cholinomimetic drug, physostigmine (0, 0.01, 0.025, 0.05 and 0.1 mg/kg, i.p.), on shuttle-box avoidance learning and electroencephalographic (EEG) activity were investigated, in two separate studies, in mice belonging to the inbred C57BL/6 (C57) and DBA/2 (DBA) strains. The results of the behavioral investigation showed a consistent, significant enhancement of avoidance performance, on the whole of 5 daily training sessions, in C57 mice treated with the lowest dose (0.01 mg/kg) and in DBA mice treated with the highest doses (0.05 and 0.1 mg/kg) of the drug. Doses higher than 0.01 mg/kg, in C57 mice, and lower than 0.05 mg/kg, in DBA mice, had no significant effect. The avoidance improvements induced by physostigmine cannot be ascribed to general behavioral activation, since the doses that increased avoidance responses did not affect or even depressed spontaneous locomotor activity. The same doses of treatment which increased avoidance responding, also induced, in the same strains, consistent enhancement of 4-7 Hz (theta) EEG band power and decrease of 7-12 Hz (alpha) band power. Results suggest that the effects induced by physostigmine on the EEG and on the shuttle-box performance of mice are related to the same neurochemical systems, and are dependent upon the interaction of the dose with specific strain sensitivity.

Animals↗

PubMed1994

Reversal of chlorpromazine-induced avoidance depression by the N-methyl-D-aspartate antagonist, dizocilpine, in mice.

The non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 (dizocilpine) was tested, alone or in combination with chlorpromazine, in mice previously trained in the shuttlebox. The lowest doses of dizocilpine (0.02 and 0.04 mg kg-1) attenuated the disrupting action of the neuroleptic (1.5 mg kg-1) on avoidance-performance, while avoidance depression induced by 1.5 and 2 mg kg-1 chlorpromazine was completely or almost completely reversed by 0.08 mg kg-1 NMDA antagonist. The highest dose (0.16 mg kg-1) of dizocilpine did not ameliorate avoidance-performance of mice receiving 2 mg kg-1 chlorpromazine, perhaps because of ataxic effects produced by the drug combination, at these doses. The results support suggestions for a potential use of NMDA antagonists in the treatment of extrapyramidal side-effects of neuroleptics.

Animals↗

PubMed1994

Effect of caffeine and nicotine on avoidance learning in mice: lack of interaction.

Tested alone, nicotine (0.25 or 0.5 mg kg-1) improved shuttle-box avoidance learning in mice of the CD-1 strain. Caffeine had no effect at doses of 2.5 and 5 mg kg-1 and impaired performance at a dose of 10 mg kg-1. Combinations of the two drugs did not increase avoidance responses more than nicotine alone, nor was nicotine able to attenuate performance depression induced by the highest dose of caffeine. Lack of drug interaction in the avoidance test contrasts with the occurrence of interactive effects of the two drugs in a locomotor activity test. When given in combination, caffeine and nicotine increased locomotor activity at doses ineffective by themselves. The results seem to indicate no advantage in combining caffeine and nicotine to improve active avoidance learning.

Animals↗

PubMed1993

Attenuation of cholinergic analgesia by nifedipine.

Nociception was tested in mice receiving oxotremorine or physostigmine either after the dihydropyridine calcium channel blocker nifedipine or the non-calcium antagonist vasodilator hydralazine. Nifedipine did not change the reaction time to thermal stimulation (tail-flick test), but attenuated the prolonging action on tail-flick latencies exerted by the two cholinomimetic agents. Hydralazine had no effect alone nor modified the action of cholinomimetics. The results suggest that attenuation of cholinergic analgesia by nifedipine might be related to not yet defined neuronal changes produced by calcium channel blockade, but changes in the pharmacokinetics of oxotremorine and physostigmine cannot be ruled out.

Analgesics↗

PubMed1993

Facilitation of shuttle-box avoidance behaviour in mice treated with nifedipine in combination with amphetamine.

The dihydropyridine calcium channel antagonist nifedipine, tested in mice of CD-1, C57BL/6 and DBA/2 strains, at doses of 2.5, 5 and 10 mg/kg IP, had no significant effect on shuttle-box avoidance acquisition. Nifedipine also failed to affect performance retention in CD-1 mice subjected to a one-trial passive avoidance task (step-through). While ineffective alone, nifedipine strongly enhanced the shuttle-box avoidance facilitating action of amphetamine (1 and 2 mg/kg IP) in low performing CD-1 mice. The results indicate that although calcium channel blockers do not affect learning in avoidance paradigms in normal animals, they can interfere with the effects of other centrally acting drugs. Calcium antagonists might interfere with neuronal changes induced by amphetamine, but at present it is difficult to explain the strong avoidance facilitation produced by combinations of nifedipine and amphetamine. A possibility that the action of nifedipine on cerebral circulation is involved in the amphetamine-nifedipine interaction cannot be excluded.

Amphetamine↗

PubMed1993

Effects of oxiracetam, physostigmine, and their combination on active and passive avoidance learning in mice.

The nootropic drug oxiracetam (50 and 100 mg/kg) had no effect on one-trial passive avoidance acquisition in CD-1 mice, while the acetylcholinesterase inhibitor physostigmine improved passive avoidance performance at doses of 0.025 and 0.05 mg/kg given either pre- or posttraining. In a multitrial avoidance task (shuttle-box), a consistent tendency to better performance was displayed by mice receiving oxiracetam (50 and 100 mg/kg) or physostigmine (0.01 and 0.025 mg/kg, but not 0.05 mg/kg). Combinations of the two drugs never improved active or passive avoidance performance more than drugs given separately. This indicates no advantage in combining nootropics and anticholinesterase inhibitors to improve learning and memory.

Animals↗

PubMed1992

Enhancement by oxiracetam of passive avoidance improvement induced by the presynaptic muscarinic antagonist secoverine in mice.

Post-trial administration of secoverine (0.5, 1 and 2.5 mg/kg), a presynaptic muscarinic blocker, improved retention in mice tested in a passive avoidance task. The nootropic drug oxiracetam (50 mg/kg), given before both acquisition and retention trial, had no effect alone, but significantly enhanced secoverine improving effects. Performance improvements were also found in combining ineffective doses of the two compounds. Even if not necessarily through a direct and specific action, oxiracetam might activate cholinergic function. Thus, performance improvements resulting from the combination of oxiracetam and secoverine may be due to a simultaneous activation of different cholinergic mechanisms.

Animals↗

PubMed1992

Neuropeptide Y-like immunoreactivity in the dogfish gastroenteropancreatic tract: light and electron microscopical study.

The 36 amino acid neuropeptide Y (NPY) has been examined in mammals and is mainly located in the nerves. Its distribution in nonmammalian vertebrate and in some invertebrate nervous systems has been confirmed. Using antisera raised to porcine NPY, NPY immunoreactivity has been localized in endocrine cells of the pancreas and gastrointestinal tract of two dogfish, Scyliorhinus stellaris and Scyliorhinus canicula. Immunostained serial sections and cross-absorption experiments with related peptides, including avian and bovine pancreatic polypeptide and peptide tyrosine tyrosine, excluded any cross-reactivity. The fine structure of the cells containing NPY-like substance is described.

Amino Acid Sequence↗

PubMed1992

Oxiracetam prevents haloperidol-induced passive avoidance impairment in mice.

The nootropic drug oxiracetam (50 mg/kg) prevented passive avoidance impairment induced by posttraining administration of haloperidol (0.25 and 0.5 mg/kg). Conversely, oxiracetam did not antagonize either locomotor depression or suppression of active avoidance responses induced by the dopamine receptor blocking agent. The results indicate that prevention of haloperidol-induced retention impairment, by oxiracetam, may be due to a not yet defined protective action, common to other nootropic agents, on different types of experimental amnesias, rather than to a specific interaction with dopaminergic mechanisms.

Animals↗

PubMed1992

Similar effects of nifedipine and hydralazine on anaesthesia and hypermotility induced by pentobarbitone in mice.

Nifedipine, a dihydropyridine calcium channel blocker, and hydralazine, a non-calcium channel antagonist vasodilatator, enhanced pentobarbitone-induced sleeping time and reversed locomotor hyperactivity induced by a subhypnotic dose of the barbiturate in mice. The similarity of the behavioural effects, exerted by nifedipine and hydralazine, suggest that haemodynamic factors may play an important role in the interaction of calcium channel antagonists with barbiturates.

Anesthesia↗

PubMed1992

Nifedipine-morphine interaction: a further investigation on nociception and locomotor activity in mice.

Nociception and locomotor activity were tested in mice (C57BL/6 and DBA/2 strains), receiving the dihydropyridine calcium-channel blocker nifedipine, alone or combined with morphine. The calcium antagonist did not change the reaction time to thermal stimulation (tail-flick test), when administered alone, but combinations of nifedipine and morphine prolonged tail-flick latencies less than did the opiate alone. Nifedipine decreased locomotion in both strains, reduced the hypermotility induced by morphine in C57 mice, and enhanced the locomotor depression induced by the opiate in DBA mice. A comparison of the effects of nifedipine with those of the non-calcium antagonist vasodilator, hydralazine, suggests that the interactions with morphine were not exclusively related to neuronal changes produced by calcium channel blockade, but also to haemodynamic factors. In fact, except for the lack of interference with morphine-induced hypermotility in C57 mice, hydralazine, given alone or in combination with morphine, produced effects similar to those of nifedipine.

Animals↗

PubMed1991

A copper-thiolate polynuclear cluster in the ACE1 transcription factor.

ACE1 is the transcriptional activator of the metallothionein (CUP1 locus) gene in Saccharomyces cerevisiae. Previous data had implicated the N-terminal domain of ACE1 as responsible for the Cu-dependent specific DNA binding. An expression system in Escherichia coli was constructed to enable the isolation of an ACE1 domain containing the DNA and Cu-binding regions. Here we report the purification and characterization of the Cu-ACE1 truncated molecule. Spectroscopic techniques showed that ACE1 contains an unusual type of DNA binding structure that is based on a polynuclear Cu(I)-cysteinyl thiolate cluster. The cluster consists of six or seven Cu(I) ions coordinated to cysteinyl thiolates in a trigonal geometry distorted from planarity. The Cu(I)-cysteine cluster of Cu-ACE1 exhibits structural properties analogous to the Cu(I)-thiolate polynuclear cluster in yeast Cu-metallothionein itself, suggesting an unusual mechanism for the evolution of this regulatory factor. The Cu cluster organizes and stabilizes the conformation of the N-terminal domain of ACE1 for specific DNA binding.

Amino Acid Sequence↗

PubMed1991

Effects of oxiracetam-nicotine combinations on active and passive avoidance learning in mice.

Tested alone, in CD-1 mice, the nootropic drug oxiracetam (50 mg/kg) improved learning in a multitrial active avoidance task (shuttle-box), but did not affect one-trial passive avoidance acquisition. Nicotine, which was ineffective at the dose of 0.25 mg/kg, improved both active and passive avoidance at the dose of 0.5 mg/kg; 1 mg/kg nicotine still exerted facilitating effects on passive avoidance, but slightly depressed shuttle-box performance. Combinations of oxiracetam and nicotine improved passive avoidance more than either drug given separately. In the active avoidance task, a combination of oxiracetam with the lower dose of nicotine exerted improving effects never observed with nicotine alone, even at higher doses. The nootropic drug also prevented the slight depressant action exerted by 1 mg/kg nicotine. Thus, contrary to what was previously supposed, at least in mice subjected to shuttle-box avoidance training, nicotinic activation does not appear as the main neurochemical mechanism involved in the action of oxiracetam. Perhaps, oxiracetam and nicotine activate different types of cholinergic mechanisms, but it cannot be excluded that other neurotransmitters, particularly catecholamines, may be involved in the avoidance facilitating effects produced by nicotine and by combinations of the two drugs.

Animals↗

PubMed1991

Avoidance learning during antidepressant withdrawal in mice.

Shuttle-box avoidance acquisition, locomotor activity and density of adrenoreceptors in the cerebral cortex have been evaluated, in CD-1 mice, during withdrawal from repeated treatment with desipramine or mianserin (5 or 14 daily injections of antidepressant drug, 10 mg kg-1). Withdrawal from mianserin did not produce any behavioural or neurochemical change. Mice withdrawn from desipramine exhibited avoidance facilitation, when training started 24 h (but not 72 or 120 h) after the last injection. Locomotor activity was not affected and no change was found in the density of beta-adrenoreceptors. An up-regulation of alpha 2- and, to a lesser extent, of alpha 1-adrenoreceptors, occurred 72 h following desipramine withdrawal. However, the assessment of the role played by these neurochemical changes in the avoidance facilitation observed during withdrawal from the antidepressant treatment requires further study.

Animals↗