Biomedical subjects
Publications and source records attributed to A Oliverio.
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.
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.
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.
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.
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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.
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.
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.
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.
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.
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.
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.
Postnatal administration of an aqueous suspension of phosphatidylserine (BC-PS) to C57BL/6 mice resulted in improvement of memory processes in adulthood, as assessed in a passive avoidance task. These findings are discussed in terms of the effects of BC-PS on cholinergic mechanisms and of cholinergic patterns of this inbred strain.
Pretreatment with naltrexone (2.5 and 5 mg/kg) prevented the decrease of 3-methoxytyramine (3-MT)/dopamine (DA) ratio induced by 2 h immobilization stress in the nucleus accumbens (NAS) of the mouse while it did not affect the stress-induced decrease of 3-MT/DA ratio in caudatus putamen (CP). Naltrexone also produced a slight antagonism of homovanillic acid (HVA)/DA ratio increase produced by stress in the frontal cortex (FC). These results point to an involvement of endogenous opioids in the effects of stress on DA metabolism in the mesolimbic system of the mouse.
1. The effects on avoidance acquisition of two nootropic drugs, oxiracetam and piracetam, were tested in mice subjected to five daily 100-trial training sessions in the shuttle-box. 2. Oxiracetam (25 or 50 mg/kg/i.p.) and piracetam (100 mg/kg/i.p.), given before each daily session, improved avoidance acquisition in the good performing BALB/c more than in the poor performing C57BL/6. In both cases avoidance facilitation was evident only if training was preceded by a five-day pretreatment. 3. Combinations of nootropics and methamphetamine increased avoidance responses in C57BL/6 mice more than drugs given separately. Conversely, no interaction occurred in a locomotor activity test. 4. Interactive effects in the learning situation, but not in a test of general activity, were also found when oxiracetam was combined with the anticholinergic agent scopolamine. 5. On the whole, the above results demonstrate facilitation of active avoidance acquisition by piracetam-like nootropic agents, but the neurochemical mechanisms involved in this action are not yet clear.
Immobilization stress induced, in mice of both C57BL/6 (C57) and DBA/2 (DBA) strains, an increase in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) and homovanillic acid (HVA)/DA ratios and a reduction of 3-methoxytyramine (3-MT)/DA ratio in the caudatus putamen (CP) and nucleus accumbens septi (NAS). These effects were already evident after 30 min stress in the NAS, while in the CP 120 min were needed in order to show the effects of stress. Immobilization did not produce any effects on dopaminergic metabolism in the frontal cortex (FC) of the C57 strain either after 30 or after 120 min stress while in mice of the DBA strain a time-dependent effect of stress on the HVA/DA ratio was evident. When B6D2F1 hybrids were considered, the effects produced by 120 min immobilization in the CP and the NAS paralleled those observed in parental strains, while in the FC 120 min stress induced the same increase of HVA observed in DBA mice, thus suggesting that the pattern of response in the FC that characterizes the DBA strain may be inherited through a dominant pattern of inheritance.
The behavioral effects of nicotine and oxotremorine were assessed in two strains of mice, C57BL/6 (C57) and DBA/2 (DBA), differing in the ontogeny of forebrain cholinergic structures. Both nicotine and oxotremorine depressed to a higher extent the behavior of DBA mice starting at day 45 of postnatal life.
The effects of prenatal exposure to stress and to naltrexone on emotional behaviors were studied in CD1 mice during ontogeny and in the adulthood. During ontogeny (a) lower body weights were initially found in pups born by mothers injected with naltrexone; (b) treatments did not affect sensory motor development except in the case of the cliff aversion reflex which occurred earlier in pups prenatally exposed to stress; (c) measures of ultrasonic vocalizations in stressful context showed that the amount of vocalizations emitted by pups born by stressed mothers was significantly higher than that emitted by pups born by naltrexone injected and control mothers (d) an examination of mother-offspring interactions on the very first day of observation indicated a consistent trend in stressed mothers to be more responsive to their pups. In adulthood, ultrasonic calls in courtship after short and long periods of isolation showed a time-dependent decrease of vocalizations in males prenatally exposed to naltrexone. These results indicate that the modifications of emotionality evident during early development are directly related to the reactivity of the mothers to the experimental treatments.