Biomedical subjects

A Oliverio

Publications and source records attributed to A Oliverio.

At least 19 recordsLinked to original sources

PubMed1999

Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice.

The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) characterized by an alkyl chain in the molecular structure which ameliorates the penetrability of the compound into the central nervous system. THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and that are much lower than the doses reported to be effective for THA in animal models. From the data reported it seems that the new compound could be interesting for therapeutic purposes.

Alzheimer Disease↗

PubMed1998

N-methyl-D-aspartate receptors in the nucleus accumbens are involved in detection of spatial novelty in mice.

The aim of this study was to investigate the role played by intra-accumbens N-methyl-D-aspartate (NMDA) receptors in spatial information encoding. For this purpose, the effect of local administration of both competitive (AP-5) and non-competitive (MK-801) NMDA antagonists was assessed in a task designed to estimate the ability of rodents to encode spatial relationships between discrete stimuli. The task consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). The results show that both doses of MK-801 (0.15 and 0.3 microg/side) induced a selective impairment in the capability of mice to detect spatial novelty. A similar effect was obtained by injecting the low dose of the competitive antagonist AP-5 (0.1 microg/side), whereas the high dose (0.15 microg/side) abolished detection of both spatial and object novelty. Taken together, these results show that intra-accumbens injections of low doses of competitive and non-competitive NMDA antagonists can produce selective deficits in processing spatial information resembling those observed after hippocampal damage. Moreover, the fact that pharmacological treatments spare memory processes involved in habituation suggests that NMDA antagonists may interfere with the formation of spatial representations rather than producing memory deficits per se.

Animals↗

PubMed1998

N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes.

In this study we report on the effects of N-methyl-D-aspartate (NMDA)- and dopamine (DA)-receptor manipulation on the modulation of one-trial inhibitory avoidance response and the encoding of spatial information, as assessed with a non-associative task. Further, a comparison with the well-known effects of the manipulation of these two receptor systems on locomotor activity is outlined. It is well assessed that NMDA-receptor blockage induces a stimulatory action on locomotor activity similar to that exerted by DA agonists. There is evidence showing that the nucleus accumbens is involved in the response induced by both NMDA antagonists and DA agonists. We show results indicating a functional interaction between these two neural systems in modulating locomotor activity, with D2 DA-receptor antagonists (sulpiride and haloperidol) being more effective than the D1 antagonist (SCH 23390) in blocking MK-801-induced locomotion. A different profile is shown in the effects of NMDA antagonists and DA agonists in the modulation of memory processes. In one-trial inhibitory avoidance response, NMDA antagonists (MK-801 and CPP) impair the response on test day, while DA agonists exert a facilitatory effect; furthermore, sub-effective doses of both D1 (SKF 23390) and D2 (quinpirole) are able to attenuate the impairing effect in a way similar to that induced by NMDA antagonists. The effects of NMDA- and DA-acting drugs on the response to spatial novelty, as assessed with a task designed to study the ability of animals to react to discrete spatial changes, are in good accord with the effects observed on passive avoidance. The results show that NMDA as well as DA antagonists, at low doses, selectively impair the reactivity of mice to spatial changes. In a last series of experiments, the possible role of NMDA receptors located in the nucleus accumbens was investigated regarding reactivity to spatial novelty. The experiments gave apparently contrasting results: while showing an impairing effect of focal administrations of NMDA antagonists in the nucleus accumbens on reactivity to spatial novelty, no effect of ibotenic acid lesions of the same structure was observed.

Animals↗

PubMed1997

Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.

Acetylcholinesterase↗

PubMed1997

Brain dopamine receptor plasticity: testing a diathesis-stress hypothesis in an animal model.

A wealth of clinical data supports a major role of genetic liability as well as of altered brain dopamine (DA) functioning in different types of behavioural disturbances. Genetic influence on behaviour involves multiple genes, rather than one or two major genes, as well as non-genetic sources of variance. Thus, in recent years, increasing attention has been devoted to the involvement of stressful experiences (life events) in the development and expression of psychopathology. Moreover, a diathesis-stress hypothesis has been proposed, which suggests that the environmental factors (stress) are not specific for a given pathology, whereas genetic factors (diathesis) are. Results obtained in an animal model offer support to this hypothesis. Indeed, mice of the C57BL/6 and DBA/2 inbred strains are equally susceptible to stress but develop different behavioural disturbances related to different alterations of brain DA receptors. Moreover, quantitative trait loci (QTL) associations in the C57 (B) x DBA (D) recombinant inbred (RI) strains indicate a number of provisional QTLs influencing the behavioural effect of stress. Finally, the results of this analysis suggest the involvement of regulatory factors related to stress response and neural or synaptic plasticity in the control of brain DA receptor plasticity.

Animals↗

PubMed1996

Time-related effects of stress on cholinergic sensitivity.

The effect of the administration of the muscarinic cholinergic agonist oxotremorine on locomotor activity was investigated in DBA/2 mice subjected to chronic restraint stress of different durations (120 min daily for 10, 14 or 18 days). Oxotremorine induced a depressant effect on locomotion, which was reduced after 10 and 14 days of restraint, but not after a 18-day restraint stress. Acetylcholine (ACh) content was significantly reduced in prefrontal cortex after 10 and 14 days of stress but returned to control values after 18 days of restraint. No changes in ACh content were observed in nucleus accumbens and striatum. These results are discussed in terms of possible changes in muscarinic receptor sensitivity.

Acetylcholine↗

PubMed1996

Dopamine-N-methyl-D-aspartate interactions in the modulation of locomotor activity and memory consolidation in mice.

This study explores the functional interaction between glutamatergic and dopaminergic systems in the modulation of two behavioral responses: locomotor activity and memory consolidation assessed with one-trial inhibitory avoidance. In agreement with previous reports, the NMDA receptor antagonist, (+)-MK-801 ((+)-5-methyl-10,11-dihydro(a,d) cyclohepten-5,10-imine hydrogen maleate), dose dependently enhanced locomotor activity in mice. The selective dopamine D1 receptor antagonist SCH 23390 at doses up to 0.05 mg/kg was unable to affect MK-801-induced locomotor activity, while (-)-sulpiride, but only at high doses (30 mg/kg), and haloperidol (0.05 mg/kg) blocked the MK-801 effect. Hypermotility induced by MK-801 was enhanced by repeated administration of haloperidol (once daily administration for 14 days of 4 mg/kg) or (-)-sulpiride (125 mg/kg), but not SCH 23390 (0.5 mg/kg). Dopamine D1 (SKF 38393)- and D2 (quinpirole)-selective agonists enhanced retention of one-trial inhibitory avoidance performance whilst NMDA receptor antagonists 3-(2-D-carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP) and MK-801 impaired it. Moreover we observed that the NMDA receptor antagonist-induced impairment of memory consolidation was attenuated by subeffective doses of SKF 38393 (5 mg/kg) and quinpirole (0.25 mg/kg). Impairment of the response induced by post-trial injections of CPP and MK-801, in the one-trial inhibitory avoidance test, was highly enhanced by 14 days of daily administration of haloperidol (4 mg/kg), sulpiride (25 mg/kg) but also SCH 23390 (0.5 mg/kg). These results suggest that different neural mechanisms underlie the functional interaction between the two neural systems in the modulation of these behavioral responses. Further, the results of the chronic study revealed a possible heterologous regulation of NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Amygdala lesions block the effect of cocaine on memory in mice.

Post-training cocaine intraperitoneal administration enhanced memory consolidation in unoperated and sham-lesioned mice tested in a one-trial inhibitory avoidance task. Bilateral electrolytical amygdala lesions blocked this effect. The results are interpreted in terms of involvement of neurotransmitter, and in particular dopaminergic, systems in the effects of cocaine on memory.

Amygdala↗

PubMed1995

Interaction between the NMDA competitive antagonist CPP and the dopaminergic system in one-trial inhibitory avoidance in C57BL/6 mice.

Post-training administration of the N-methyl-D-aspartate (NMDA) receptors antagonist CPP, at doses of 0.5 and 1.0 mg/kg, impaired, in dose-dependent fashion, retention of the inhibitory avoidance response in C57BL/6J (C57) mice. Post-training subeffective doses of selective D1 and D2 dopamine receptor agonists, were able to antagonize the action of CPP, while subeffective doses of SCH 23390 and (-) sulpiride, respectively, D1- and D2-selective antagonists, enhanced the effects of the NMDA antagonist. Furthermore, subchronic blockade of dopamine receptor through a 10-day daily treatment with 4 mg/kg of haloperidol induced an adaptation of both the dopaminergic and the glutamatergic system. The possible upregulation of D2 receptors, in response to repeated injection with haloperidol is shown in the one-trial inhibitory avoidance by an increased response to the D2 agonist. In addition, our data show a potentiation of CPP effects after the same treatment. These results suggest a complex interaction between dopamine and glutamate in modulating one-trial inhibitory avoidance behavior in mice.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Chronic treatment with MK-801 affects the behavioral response to both D1 and D2 dopamine agonist in the one-trial inhibitory avoidance.

Post-training administration of the N-methyl-D-aspartate (NMDA) antagonists CPP (0.5 and 1.0 mg/kg) and MK-801 (0.25 and 0.5 mg/kg) impaired, in a dose dependent fashion, the one-trial inhibitory avoidance response in NMRI mice. The D1 dopamine (DA) agonist SKF 38393 (10 and 20 mg/kg) and the D2 agonist quinpirole (0.5 and 1.0 mg/kg) instead facilitate the response in the same behavioral paradigm. Sub-chronic blockade of NMDA receptors with MK-801 (0.25 mg/kg once a day for 14 days) did not change the response to both competitive (CPP) and non-competitive (MK-801) NMDA antagonists. The same chronic treatment with MK-801 induced an increased response to both SKF 38393 and quinpirole. These data suggest that repeated administration of MK-801 induce an upregulation of both D1 and D2 DA receptors without affecting NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.

Animals↗

PubMed1993

A pharmacological discrimination of two behavioral forms of the paradise fish (Macropodus opercularis).

Intracranial injections of 5 micrograms/fish (equivalent to 2 nmol/g) of the dopamine agonist Apomorphine into the paradise fish brain considerably decrease the occurrence of escape behavior with a parallel increase of time spent in swimming. All other elements of the behavioral repertoire are unaffected. The simultaneous administration of 0.5 micrograms/fish (equivalent to 0.15 nmol/g) of the dopamine antagonist Pimozide abolishes this effect. In a second experiment a dose dependent decrease in escape behavior was obtained with a parallel increase of swimming. On the bases of these pharmacological data it is concluded that the escape and the swimming reactions are truly independent units but their regulation might be closely related.

Animals↗

PubMed1992

Autoradiography of muscarinic cholinergic receptors in cortical and subcortical brain regions of C57BL/6 and DBA/2 mice.

Mice of the inbred strains C57BL/6 and DBA/2 show strain-dependent behavioural differences which have been correlated with variations in brain cholinergic systems. In the present study, the density of muscarinic cholinergic receptors in both strains of mice was determined by autoradiographic methods using [3H]quinuclidinyl benzilate (QNB) and [3H]pirenzepine as ligands. C57BL/6 mice showed a significantly lower [3H]QNB binding level in the frontal cortex by one third as compared to DBA/2 mice. In the striatum and the cholinergic pontomesencephalic nucleus laterodorsalis tegmenti the [3H]QNB binding was lower in C57BL/6 by 28% and 31%, respectively. The [3H]pirenzepine binding level was found to be significantly higher in C57BL/6 temporal cortex (by 22%). These results are discussed in relation to interstrain differences in cholinergic cell density and in the activity of cholinergic enzymes.

Animals↗

PubMed1992

Nonhuman behavioral models in the genetics of disturbed behavior.

The development of the association method in which genetic markers match quantitative traits had led to quantitative trait loci (QTL) interval mapping. The association method has been extensively used in animal behavior genetics. Animal research allows more suitable linkage studies and detailed assessment of cellular and subcellular components of the central nervous system that may play a crucial role in the development susceptibility to behavioral disorders. Moreover, experimental designs in the laboratory setting allow genotype x environment interactions to be controlled, thus possibly providing more information on the role of nongenetic factors in gene expression. Experimental results are discussed which indicate that animal studies will provide a sort of test for hypotheses arising in clinical settings, allowing gene-product and product-behavior pathways to be examined at molecular levels when the gene accounts for a very small amount of genetic variance. In such a perspective, new molecular biology approaches and behavior genetics in nonhuman species could provide useful tools in the assessment of the genetic as well as nongenetic factors that lead to psychopathology.

Affective Disorders, Psychotic↗

PubMed1991

Effects of acute and chronic stress and of genotype on oxotremorine-induced locomotor depression of mice.

The locomotor behavior of unstressed and stressed mice of two inbred strains, DBA/2 and C57/BL6, was investigated. Animals were tested in a toggle-floor box apparatus, 30 min after saline or oxotremorine treatment (ip). A dose of oxotremorine that did not depress the activity of naïve mice (0.01 mg/kg) was chosen. Stressed mice were injected 24 h after either a single 2-h stress session (acute stress) or the last of 14 daily stress sessions of tube restraining (chronic stress). Acute stress did not modify the depressant effect of oxotremorine on locomotor behavior in either strain. On the contrary, chronic stress induced a clear sensitization of DBA but not C57 mice to the depressant effect of oxotremorine. These findings show that chronic stress may result in modifications of the cholinergic function, and its behavioral correlates, and that these changes are modulated by the genetic makeup.

Animals↗

PubMed1990

Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse.

Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters.

Animals↗

PubMed1990

Effect of chronic GM1 ganglioside administration on passive avoidance retention in mice.

Chronic administration of GM1 ganglioside to C57BL/6 mice during development improved passive avoidance retention. A significant weight increase was also evident in the treated animals in comparison with the control group. The results are discussed in terms of the possible effects exerted by GM1 upon the cholinergic mechanisms of this inbred strain.

Animals↗

PubMed1990

Different levels of acetylcholinesterase and choline acetyltransferase activities in C57Bl/6 and DBA/2 mice are not accompanied with different density of cortical acetylcholinesterase reactive fibers.

Mice of the inbred strains C57B1/6 and DBA/2 show strain-dependent behavioural differences which have been correlated with variations in the organization of brain cholinergic systems. The aim of our study was to analyse the extent of cholinergic interstrain differences in circumscript brain regions of C57B1/6 and DBA/2 mice. The biochemical determination of choline acetyltransferase and acetylcholinesterase in cortical areas, basal forebrain and striatum showed significantly lower enzyme activities in most of the regions of C57B1/6 mice. The deficit was most pronounced in the basal forebrain/diagonal band, in the piriform cortex, and striatum. The density of acetylcholinesterase-stained cortical fibres did not reflect the biochemical interstrain differences. This may be due to a different enzyme content in the nerve fibers of the two mice strains. The previous findings are discussed in terms of brain cholinergic disorders in which the extent of damage but also the proportions of regional deficits may influence the pattern of behavioural dysfunctions.

Acetylcholinesterase↗