Biomedical subjects

M M Bernardi

Publications and source records attributed to M M Bernardi.

At least 19 recordsLinked to original sources

PubMed2005

Prenatal treatment with picrotoxin promotes heterotypical sexual behavioral and neurochemical changes in male rat offspring.

The effects of maternal prenatal exposure to picrotoxin (0.75 mg/kg S.C. days 16-19 of pregnancy) in male rat offspring were observed. Adult sexually experienced and inexperienced animals were evaluated for heterotypical sexual behavior, as well as the testosterone plasma levels and striatal neurotransmitters. In relation to sexual behavior and analysis of sexual organs, the results showed that animals treated with picrotoxin exhibited a more intense reproductive behavior, and this could be expressed by a significant decrease in the number of mounts and intromissions and increase in the numbers of ejaculation, showed that these males are most motivate for sexual behavior. Testosterone levels as well as weight for sexual organs did not differ from control group. The neurochemical analysis showed that picrotoxin did not alter DA, 5-HT, 5-HIAA and GABA in animals. The DOPAC/DA and HVA/DA relation showed that the treatment increased the DA system activity in animals sexually experienced, as well as promote a decrease in 5-HT/5-HIAA relation, that is known was an inhibitory neurotransmitter system, blockade a male sexual behavior. There are no alterations observed in GABA levels. It's could be explained by suggests that picrotoxin modification DA system activity through GABAergic system, permitting that DA system to be freely active and facilitate the heterotypical behavior of male rats. These results show that the maternal prenatal exposure to picrotoxin produced changes in the neurochemical and sexual behavior of the adult male rats. Also previous heterotypical experience leads to changes in biogenic amine concentrations in these animals.

Animals↗

PubMed2005

Analysis of the toxic potential of Palicourea corymbifera (Müll. Arg.) Standl. in laboratory animals.

Palicourea species may produce bovine toxicity. Palicourea corymbifera grows in terra firme forests within the Amazon rain forest and in Tropical America, particularly in spots that gave place to gazing areas. The lyophilized extract done with the aerial organs of P. corymbifera were analyzed in male and female mice. Results revealed a significant toxicity: LD50 was 1.10 (1.04-1.15)g/kg for male mice, and 1.05 (1.00-1.10)g/kg for female mice. Locomotion was affected as well as there were reflexes linked to environmental stimuli in addition to changes in posture. Progressive central nervous system stimulus signs such as trembling and convulsions were detected, the latter followed by the animal's death. Macroscopic histopathological exams performed on the liver, kidneys and lungs of mice submitted to necropsy did not indicate the existence of lesions. General activity of animals, measured in an open field, was reduced as a result of the administration of the extract. Duration of locomotion and rearing frequency were reduced, in opposition to an increase in the duration of immobility. Thin layer chromatography analysis showed that monofluoroacetic acid is present in the lyophilized extract, but other qualitative techniques as gas chromatography/mass spectrometry and 19F nuclear magnetic resonance showed that the MFAA was not present in the extract, and that the toxicity is related to other compound, although the toxic profile is very similar to that of MFAA. P. corymbifera was shown to be significantly toxic to laboratory animals and investigation of the possible toxic substance shall be done.

Animals↗

PubMed2005

Rats exposed to Solanum lycocarpum fruit in utero and during lactation: neurochemical, behavioral and histopathological effects.

Solanum lycocarpum St. Hil (Solanaceae) is a native shrub very common in the Brazilian savannah. This plant contains steroidal glycoalkaloids that can be transformed into an intermediate for steroidal drug production. In this way, it is very possible that these glycoalkaloids and its aglycone, once in the body by ingestion of S. lycocarpum fruits, may act by disrupting the endocrine system. Because its fruits may be consumed by pregnant animals in the fields, the present study determined the possible toxic effects of exposure to S. lycocarpum fruit (10% added in the diet) from gestation day (GD) 6 to postnatal day (PND) 07 in rat dams. The unripe fruits contained 0.6% of solamargine and 0.9% of solasonine. S. lycocarpum, 10% in the diet, during gestation and the beginning of lactation reduced intrauterine growth. In addition, 20% of the treated dams showed some dead pups at birth. Reduced body weight was observed from birth through adulthood in male and female offspring exposed to 10% S. lycocarpum unripe fruits. During adulthood, female offspring showed impaired sexual behavior and male offspring showed prominent degeneration of testis germinative cells, characterized by a reduced number of germ cells and vacuolation. Also, the exposed offspring showed reduced hypothalamic norepinephrine (NOR), vanillylmandelic acid (VMA), 3-methoxy-4-hydrophenylglycol (MHPG) and homovanillic acid (HVA) levels, and reduced striatum NOR, HVA, VMA, MHPG, dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolacetic acid (5-HIAA) levels. These results suggest that the fruit may act as an estrogen, with a long-term effect, impairing the receptive lordosis behavior of female offspring and promoting testis abnormalities in male offspring at adulthood. Finally, it appears to disrupt brain organization since important central monoamine level alterations were also observed.

Animals↗

PubMed2005

Toxicity of cadmium in Japanese quail: evaluation of body weight, hepatic and renal function, and cellular immune response.

Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TN alpha and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure.

Alanine Transaminase↗

PubMed2005

Perinatal maternal exposure to picrotoxin: effects on sexual behavior in female rat offspring.

A previous study in our laboratory showed that perinatal maternal picrotoxin exposure (0.75 mg/kg) in rats improved heterosexual behavior in male offspring. In the present study, we examined the effects of this maternal treatment on sexual behavior in the female offspring. The dams received 0.75 mg/kg picrotoxin treatment (PT) once a day on the 18th and 21st day of pregnancy, 2 h after parturition and once a day during the first 4 days of lactation. The results showed that (1) at birth, the body weight and anogenital distance were not modified by treatment; (2) female sexual behavior was improved in experimental animals. These results demonstrate that perinatal picrotoxin exposure improves adult sexual behavior in female rat offspring as suggested by increase in the lordosis quotient.

Animals↗

PubMed2003

Effects of maternal exposure to picrotoxin during lactation on physical and reflex development, square crossing and sexual behavior of rat offspring.

The effects of maternal exposure during the first 10 days of lactation to picrotoxin (0.75 mg/kg sc) on maternal behavior, offspring physical and neurobehavioral development as well as sexual behavior were studied. Results showed that (1) dam food and water consumption, maternal behavior and body weight were not different between control and experimental animals, (2) male and female pup body weight and the development of physical landmarks did no differ between control and experimental groups, (3) negative geotaxis was improved in female experimental offspring and palmar grasp reflex did not differ between groups, (4) at 75 days of age the square crossing by female rats of the experimental group was increased in relation to the control group; no differences were observed between male control and experimental animals, (5) male experimental rats exhibited a significant increase in the number of mounts, intromissions and ejaculations parallel to a decrease in latency to first mount, intromissions and ejaculation as well as in the latencies of first postejaculatory mount and intromission and (6) the intromission frequency per minute (hit rate) was increased in these animals. These results suggest that postnatal exposure to picrotoxin improved the sexual behavior of rats. Three hypotheses were proposed to explain the mechanisms underlying this effect: (1) the development of subsensitivity of GABAergic receptors, (2) an interference with early receptor development or (3) with neurotransmitter balance, mainly involving the dopaminergic system.

Animals↗

PubMed2003

Toxicological evaluations of long-term consumption of Solanum lycocarpum St. Hill fruits in male and female adult rats.

Solanum lycocarpum St. Hill is a common plant in the Brazilian savanna. This plant contains an alkaloid with stereospecific configuration to the synthesis of steroid hormones. Because the plant may be consumed long-term, the present study was undertaken to determine the possible toxic effects of S. lycocarpum fruit ingestion (3% added to the diet) on male (60 days of administration) and female (37 days) adult rats. Few significant differences in body weight and consumption of food and water, no significant differences in male and female weight gain or estrous cycle were detected. Female treated rats showed a significant reduction in uterus and liver weights; however, no significant differences were observed in other organ (adrenal, liver, seminal vesicle, testicle and ovary) weights in either sex. Additionally blood enzymes and proteins evaluated were not affected by treatment with 3% S. lycocarpum added to the diet. The present data, however, show sex-related differences in S. lycocarpum toxicity. Thus, other studies have to be conducted to better investigate female toxicity and other toxic effects of higher levels of exposure to this plant.

Administration, Oral↗

PubMed2002

Possible anxiolytic effects of ivermectin in rats.

Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.

Animals↗

PubMed2001

Tolerance to the antinociceptive effect of Crotalus durissus terrificus snake venom in mice is mediated by pharmacodynamic mechanisms.

Crotalus durissus terrificus venom exerts central and peripheral antinociceptive effect mediated by opioid receptors. The present work investigated the tolerance to the antinociceptive effect of the venom and characterised the mechanisms involved in this phenomenon. The hot plate test, applied in mice, was used for pain threshold determination. The venom (200 microg/kg) was administered by oral route, daily, for 14 days, and the nociceptive test was applied before and on days 1, 7 and 14 of the treatment. Prolonged treatment with venom lead to the development of tolerance to the antinociceptive effect. Tolerant animals exhibited increased sodium pentobarbital-induced sleeping time, although total hepatic microsomal cytochrome P450 was not altered. The antinociceptive effect of a single dose of venom (200 microg/kg) is mediated by kappa opioid receptors. Mice long-term-treated with venom showed cross-tolerance to U-TRANS, an agonist of kappa-opioid receptor, but not to morphine or DAMGO, two mu-opioid receptor agonists. Prolonged administration of venom did not cause symptoms of abstinence syndrome. These data indicate that prolonged treatment with C. durissus terrificus venom induces tolerance to the antinociceptive effect and that pharmacodynamic mechanisms are involved in the genesis of this phenomenon.

Analgesics↗

PubMed2001

Effects of dopamine receptor antagonists on ongoing maternal behavior in rats.

The effects of different peripheral doses of four dopamine (DA) receptor antagonists on general activity and maternal behavior were examined in lactating female rats. Administration of the classic D1-like and D2-like DA receptor blocker haloperidol (0.1 and 0.05 mg/kg) disrupted pup retrieval and nest-building behaviors and reduced motor activity. Pimozide (0.5 and 0.2 mg/kg), which has more affinity for DA D2-like receptors, mildly disrupted pup retrieval while showing no significant influence on open-field behaviors. The putative DA D(4) receptor blocker, clozapine (1.5 and 1.0 mg/kg) reduced motor activity significantly, while only 1.0 mg/kg dose significantly decreased percent of rats displaying nest building. The DA D1-like receptor blocker SKF-83566 (0.2 and 0.1 mg/kg) significantly reduced pup retrieval, nest building and motor activity. These results suggest a role for DA receptors in ongoing maternal behavior that correlates directly with general activity.

Adult↗

PubMed2000

Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations.

Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyric acid (GABA) neurotransmission. Some behavioral manifestations are related with GABAergic neurotransmissions as anxiety and seizures. The objective of the present study was to examine the possible central nervous system (CNS) effects of doramectin (100, 300 and 1000 microg/kg, SC) in rats, using anxiety behavioral models, susceptibility to seizures and central neurotransmitter evaluations. The open-field results showed (i) few alterations in locomotion frequency; (ii) a biphasic effect on rearing frequency that may be the consequence of least habituation in open-field; (iii) the reduction of grooming durations might be attributed to a possible anxiolytic effect of doramectin since GABAergic agonists reduced this parameter in apparatus. Our data in the hole board showed no effects in locomotion and rearing frequencies but increased head dipping frequency of rats administered doramectin similarly to anxiolytic drugs. In plus-maze test, doramectin administration increased the number of entries and time into open arms, indicating also an anxiolytic effect. Doramectin protected animals from convulsant effects of picrotoxin, indicative of an anxiolytic pharmacological profile of a drug with GABAergic properties. The alterations observed in central dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the consequence of reinforcement in central GABAergic neurotransmission induced by doramectin. The present results suggest that doramectin has the pharmacological profile of an anxiolytic/anticonvulsant drug with GABAergic properties.

Animals↗

PubMed2000

Croton zehntneri essential oil: effects on behavioral models related to depression and anxiety.

Croton zehntneri (Cz), a popular plant used to treat "nervous disturbance", contains a complex mixture of compounds, including substances exhibiting central nervous system activity. The effects of Cz essential oil administration (p.o.) on the rat's central nervous system were studied in behavioral models used to evaluate anxiety and antidepressive drugs. The results showed that administration of Cz essential oil: 1) increased the immobility duration measured in the forced swimming test as compared to control group (control = 89.8 +/- 45.8; 1 microl = 153.0 +/- 48.7; 3 microl = 157.4 +/- 45.3; 10 microl = 145.3 +/- 51.0); 2) reduced the locomotion frequency observed in the open field (control = 62.5 +/- 22.7; 3 microl = 38.0 +/- 13.5; 10 microl = 39.2 +/- 22.2); 3) had no effect on the experimental group (1 microl) observed in open field; 4) had no effect on animals tested in social interactions, plus-maze and holeboard tests. These data suggest that Cz oil produced central depressor effects in rats without any anxiety alterations. These results may explain the popular use of this plant in Brazilian folk medicine for treating "nervous disturbances".

Animals↗

PubMed1999

Possible anxiogenic effects of fenvalerate, a type II pyrethroid pesticide, in rats.

Pyrethroids are insecticides extensively used to control pests around houses as well as in agriculture. It has been suggested that type II pyrethroids may act on GABA receptors as benzodiazepine antagonists. Because benzodiazepines are used in anxiety, the present study was undertaken to investigate the possible anxiogenic effects of fenvalerate, a type II pyrethroid, in rats. Behavior in the open-field, social interaction, plus-maze behavior, and one-way passive avoidance were studied in rats orally treated with 1, 10, or 30 mg/kg fenvalerate. This pyrethroid reduced locomotion and rearing frequencies and increased immobility duration. Ten and 30 mg/kg of fenvalerate reduced social interaction, whereas the 1 mg/kg dose had no effect on this behavior. Fenvalerate administration did not change the plus-maze behavior of rats. Pretraining administration (1, 10, and 30 mg/kg) did not modify the behavior of rats during the training session of a passive avoidance task, while in the test session 10 mg/kg fenvalerate caused an increase in the crossing latency, and the 30 mg/kg dose reduced this parameter and increased the percent of animals crossing to the shock compartment. The behavioral alterations observed in this study suggest that fenvalerate has an anxiolytic effect on rats.

Animals↗

PubMed1998

Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system.

The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.

Animals↗

PubMed1998

The antinociceptive effect of Crotalus durissus terrificus snake venom is mainly due to a supraspinally integrated response.

The antinociceptive effect of Crotalus durissus terrificus snake venom, previously demonstrated in the hot-plate test, was investigated in mice using the tail-flick model. The venom, administered by the intraperitoneal, subcutaneous or oral route, did not modify the basal latency time to the noxious stimulus and the association of the venom with morphine did not alter the opioid analgesic effect of this drug. These data indicate that the antinociceptive effect of the venom is mainly due to a supraspinally integrated response.

Animals↗

PubMed1998

Perinatal treatment with picrotoxin induces sexual, behavioral, and neuroendocrine changes in male rats.

The effects of maternal exposure to picrotoxin (PT) during the prenatal and postnatal periods of sexual brain differentiation were studied. Behavioral (sexual behavior), physical (sexual maturation, body, and organ weights) and neurochemical (striatal and hypothalamic monoamine and respective metabolite levels) data were assessed in the offspring of PT-treated dams. The following results were obtained: 1) sexual maturation as measured by the day of testis descent and testis weight comparison was unchanged; 2) a decrease in male sexual behavior occurred, as well as a decrease in body, ductus deferens, and seminal vesicle weights and in plasma testosterone levels of adult male offspring; 3) striatal dopamine (DA) and homovanillic acid (HVA) levels were decreased and hypothalamic norepinephrine (NE) levels were increased. These results indicate that perinatal exposure to PT during the critical periods of male brain sexual differentiation has long-term effects on the reproductive physiology and behavior of male rats.

Animals↗

PubMed1997

Influence of lactation on motor activity and elevated plus maze behavior.

Lactating rats show less noise-induced freezing and fewer inhibitory responses on the 6th day post-delivery when submitted to water and food deprivation in a classical conflict paradigm. Lactating mice go more often to the illuminated chamber in a light-dark cage and stay longer in it than virgin females. The present study was designed to assess the influence of this physiological state, i.e. lactation, on the elevated plus maze (EPM) and open-field behavior in adult female rats. Total (TL) and central (CL) locomotion and rearing (RF) frequencies were measured in an open-field. Number of entries into the open and closed arms as well as the time spent in each of these arms were measured in the EPM. percent time spent and number of entries into the open arms were calculated and compared. In the open-field, TL was significantly decreased (115 +/- 10.6 vs 150 +/- 11.6) while CL and RF did not differ from those presented by virgin rats. In the EPM, lactating rats displayed a significant reduction in percent time spent (10.9 +/- 1.5 vs 17.4 +/- 2.3) in the open arms as well as a tendency to a reduction in percent entries into the open arms (35.7 +/- 4.7 vs 45.7 +/- 4.3). These results show that the physiological state of lactation modulates the open-field and EPM behaviors in rats.

Animals↗

PubMed1996

Perinatal astemizole exposure in the rat throughout gestation: long-term behavioral and anatomic effects associated with reproduction.

Astemizole (ATZ), a non-sedative antihistamine, which antagonize histamine at the level of H1 receptor, was administered daily to female Wistar rats as a 10-mg/kg dose throughout pregnancy. ATZ exposure reduced offspring body weight and delayed the pinna detachment and startle reflex without any modification of dams body weight during gestation. Long-term disruption of male reproductive behavior was seen in experimental animals, whereas female sexual behavior was not modified. In addition, no motor alterations were observed in female or males in adulthood. Testis wet weight was reduced, but no modifications were detected in vasa deferentia or seminal vesicle. We proposed that ATZ administration during pregnancy causes several effects mainly of a sexual nature by interfering either with the hormonal mechanism involved in the central nervous system masculinization or by a direct action of the drug on pups during the development.

Animals↗