[Influence of bromazepam on the subacute toxicity and ECG changes caused by nicotine in guinea pigs].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to V Cuomo.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D1 receptor sites in the caudate putamen. Conversely, no significant changes were observed in D2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D1 receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.
This article reviews the literature and presents some unpublished data on the CNS effects of alcohol at doses not producing tolerance and dependence. The available evidence indicates that the effect of low doses of ethanol may qualitatively differ from those produced in animal models mimicking alcoholism. For example, rats exposed for two months to alcohol in drinking water at a concentration (3%) not inducing tolerance or dependence, as assessed by lack of withdrawal signs upon treatment suspension, appear to be less stressed in the two-way avoidance-learning tests. Accordingly, the treated rats perform better and learn faster than sucrose-fed controls, while this behavior is disrupted by high levels of ethanol intake. These initial observations suggest that discontinuity may exist between the effects of low and high doses of this substance and underscore the need to expand research on the effects of alcohol on the CNS to include the bottom end of the dose-response curve.
Ultrasonic calls are emitted by many species of rodents in a variety of situations. In particular, infants commonly emit such calls when removed from the nest; the rate and intensity of calling are related to the degree of development of homoiothermy. The relevant biological significance of these signals is documented by their capability to promote parental behaviour, such as maternal retrieval. There is recent evidence that ultrasonic vocalization in rodent pups could be valuable as a bioassay in Behavioural Toxicology. In particular, the results of our recent studies together with those of other authors suggest that ultrasonic calls emitted by infant rats could be considered a useful test in detecting subtle effects of adverse treatment during development.
Early postnatal exposure to morphine significantly influenced the ultrasonic vocalization of rat pups removed from their nest. In particular, a significant decrease in the rate of calling, sound pressure level and range of frequency was found in morphine-treated animals; moreover, the duration of calls was significantly increased by morphine administration. Conversely, neither beta-casomorphins (beta CMS), which are opioid peptides derived from the enzymatic digestion of milk protein (beta-casein), nor an opioid antagonist, like naloxone, significantly affected ultrasonic emission. The results are discussed with particular reference to the role of the opioid system in separation distress-induced vocalization in young animals.
Five laboratories collaborated in the evaluation of detection limits of different testing concepts in behavioral teratology. In one laboratory, rat dams were treated by gavage with five doses of methylmercury (0.0, 0.25, 0.05, 0.5, and 5.0 mg/kg/day). The treatment period was restricted to days 6 to 9 of gestation. The usual reproduction parameters were assessed in the dams. The offspring (88-99 per group) were subjected to a routine developmental and behavioral testing battery. After completion of these tests, random samples of the animals were further investigated in four other laboratories using the following techniques: auditory startle habituation, visual discrimination and figure-8 activity monitor; wheel-shaped activity monitor and spatial alternation operant conditioning; two-compartment locomotor activity, passive avoidance and male ultrasonic vocalization during sexual behavior; assays of the weight of different brain areas, their glial fibrillary acidic (GFA) protein and S-100 protein concentration. The following dose-dependent effects were noted in ascending dose sensitivity order: delayed vaginal opening; increased and more variable passiveness in spatial alternation; impaired swimming behavior, increased GFA protein concentration in the cerebellar vermis; increased auditory startle amplitude, decreased intertrial interval pokes in the visual discrimination test, increased percentage of visits in passive area of figure-8 activity monitor, increased path iteration frequencies and decreased local activity in the wheel-shaped activity monitor, decreased locomotor activity in the two-compartment monitor, increased cerebellar vermis weight, and decreased S-100 protein in the hippocampus. Therefore, this study showed comparable sensitivities for the behavioral testing battery, for some automated multiparametric test systems and for the neurochemical assays.
On day 15 of gestation, pregnant Sprague-Dawley rats were orally treated by gavage with 8 mg/kg of methyl mercury (MMC). At day 1 of postnatal life the levels of MMC in whole brain of exposed pups were found to be about 100 times higher than those of saline-exposed rats, while they were near to the control values at 21 days and practically normal at 60 days of age. Behavioral experiments showed that exposure to MMC in late gestation did not affect at any tested time (14, 21 and 60 days) locomotor activity or development of ultrasonic vocalization. An increased response to a challenge dose of amphetamine was, however, detected in MMC-exposed pups at day 14. This phenomenon was no longer evident at day 21 and 60 of age. In parallel, an increased density of dopamine receptors was found in the striatum at 14, but not at 21 and 60, days of age. From these data, we tentatively suggest that a high level of MMC induces a transient phenomenon of disuse-supersensitivity of the dopaminergic system. Moreover, further evidence that acute MMC exposure during prenatal life might induce permanent disturbances in learning and memory which could be partially related to a reduced functional activity of the glutamatergic system is provided.
Explore the source record for details and available documents.
Few studies have investigated neurobehavioral and neurochemical consequences of chronic consumption of low doses of ethanol. The present study shows that in rats exposure to 3% ethanol (v/v in drinking water) for 2 months decreased both calcium-dependent and -independent protein kinase C (PKC) activities in the cortex and in the hippocampus. This treatment also reduced ultrasonic calls (UCs), an index of emotional and motivational states of the animal. In addition, at cortical level of ethanol-treated rats, we observed a correlation between calcium-dependent activities and UCs. These results suggest that nonaddicting doses of ethanol affect brain PKC activities and that this enzyme may be involved in the ethanol modulation of emotional and motivational behaviors.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Myelinated nerve fibres isolated from Wistar rats chronically exposed to 2,5-hexanedione (0.8 ml/kg/day, intraperitoneally) over a period of 20 days, were stained with lectin-horseradish peroxidase conjugates. The lectins with high affinity for terminal D-galactopyranosyl residues, Bandeiraea simplicifolia-B4 (BSA I-B4) and peanut agglutinin (PNA), showed glycoconjugates in the control nodes of Ranvier. In the treated animals, application of PNA-HRP caused weak reactivity to the node of Ranvier; digestion with sialidase prior to the application of PNA-HRP conjugate enhanced reactivity, thus revealing the presence of a sialoglycoprotein. The results indicate that glycoconjugates of the Ranvier node undergo a rearrangement during exposure to 2,5-hexanedione. In particular, neutral glycoproteins with terminal galactose are replaced by sialoglycoproteins. These findings are consistent with the proposed role of polysialic acid as a regulator of axonal behaviour during regeneration.
The intensity of apomorphine (1-2 mg/kg)-induced stereotyped behaviour was significantly lower in 60 day old offspring of rats treated with haloperidol during pregnancy (0.5 mg/kg SC for 15 days, beginning on day 4 after conception) than in vehicle-exposed animals. Moreover, at 60 days of age, apomorphine (1-2 mg/kg)-induced inhibition of locomotor activity was much less marked in haloperidol-pretreated than in vehicle-pretreated rats. Conversely, our previous data showed that behavioural supersensitivity to apomorphine (1-2 mg/kg) was still present 40 days after the last administration of haloperidol, if the animals received the drug (0.5 mg/kg SC) from birth to 20 days of age. Finally, at 80 days of age, animals prenatally exposed to haloperidol were subjected to a differential reinforcement of low rates schedule (DRL-15 sec). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in control animals than in haloperidol-pretreated rats. In this regard, we previously showed that early postnatal exposure to the neuroleptic also impairs the acquisition of the DRL schedule in adult rats. These data confirm and extend the differences in behavioural consequences of prenatal and early postnatal exposure to haloperidol, and further point to the usefulness of DRL task in the evaluation of subtle behavioural changes induced by psychotropic drugs in the absence of overt signs of neurotoxicity.
Explore the source record for details and available documents.
On day 8 of gestation, pregnant Sprague-Dawley rats were intubated with 8 mg/kg of methyl mercury (MM). At 15 days of age, stereotyped sniffing was elicited by a challenge dose of apomorphine (1 mg/kg) only in pups prenatally exposed to MM; furthermore, at 22 days of age, the stereotyped behaviour induced by apomorphine (0.5-1 mg/kg) was significantly potentiated in MM-pretreated animals. Neurochemical data showed that at 22 days of age there was a significant increase of 3H-spiroperidol binding sites in striatal membranes of MM-pretreated rats. At 40 and 60 days of age, these behavioural and neurochemical changes were absent. On the other hand, prenatal exposure to MM influenced neither the effects of a challenge dose of clonidine (0.025 mg/kg) on locomotor activity nor the affinity and the density of alpha-2 adreno-receptors in cortex of 15, 22, 40 and 60 day old rats. The behavioural alterations in the response to apomorphine presumably result from an enhancement of dopamine binding sites induced by MM. Finally, our data further confirm that prenatal MM induces long lasting behavioural alterations which can be accurately displayed by using passive avoidance procedures.