Biomedical subjects

J C Flório

Publications and source records attributed to J C Flório.

9 recordsLinked to original sources

PubMed2005

A comparative study of morphine treatment regimen prior to mating and during late pregnancy.

Pre-mating treatment of female rats with morphine may have long-term effects. In this study, we analyzed the effects of two types of morphine sulfate pre-treatment: during pre-mating (5.0 mg/kg on alternate days for a total of seven doses) and during pregnancy (3.5 mg/(kgday) for 5 days starting on day 17 of pregnancy during early lactation. In order to evaluate possible morphine-induced behavioral changes, dams were tested for maternal behavior and locomotor activity during early lactation, and striatal and hypothalamic concentrations of dopamine and their metabolites and serum levels of corticosterone were measured. Maternal behavior was disrupted only in animals treated with morphine sulfate during pregnancy and challenged acutely (1.5 mg/kg) during lactation. Pre-mating treatment with morphine sulfate-induced changes in responses with increased locomotor activity, striatal dopamine turnover and serum corticosterone levels. None of these parameters were affected by morphine sulfate pre-treatment during late pregnancy. These data suggest that morphine has specific long-term and sometimes addictive-like effects on actively reproductive female animals that vary with the pre-treatment period, late pregnancy being particularly sensitive for effects on maternal behavior.

3,4-Dihydroxyphenylacetic Acid↗

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↗

PubMed2001

Stimulation of either cholecystokinin receptor subtype reduces while antagonists potentiate or sensitize a morphine-induced excitatory response.

Cholecystokinin peptides (CCK) have been shown to antagonize many opioid-mediated effects. The present study was undertaken to determine whether peripheral injections of cholecystokinin sulphated octapeptide (CCK8), cholecystokinin tetrapeptide (CCK4), the CCK(1) (lorglumide) and the CCK(2) (PD-135,158 and LY-225910) receptor antagonists can influence a classic morphine excitatory effect, i.e. the display of Straub tail reaction in mice (STR). A total of 570 female Balb/C mice were tested. Experiment 1 was undertaken to determine whether i.p. injections of CCK8 or CCK4 can influence STR. Each animal was treated with i.p. injections of saline or CCK8 (10 and 20 nmol/kg) or CCK4 (20 and 40 nmol/kg). After 30 min all animals received an i.p. injection of morphine hydrochloride (10.0 mg/kg). The highest doses of both CCK8 (35% STR) and CCK4 (40% STR) significantly reduced STR as compared to saline (85% STR) treated mice (Fisher test; P < 0.01). In experiment 2 each animal was treated with ip injections of saline or 1.0 mg/kg lorglumide or PD-135,158 fifteen minutes before an injection of morphine at doses ranging from 1.0 to 50.0 mg/kg. In experiment 3 animals were treated with injections of saline, 0.1 or 10.0 mg/kg lorglumide or LY-225910 before an injection of a fixed MC dose (2.0 mg/kg). Both lorglumide and PD-135,158 induced a significant shift to the left in the morphine dose-response curves as well as a significant decrease in ED50 of the STR. ED50 for lorglumide was significantly lower than ED50 for PD-135,158. Both doses of lorglumide and the highest dose of LY-225910 significantly increased the percent of animals displaying STR. Experiment 4 was undertaken to determine whether repeated peripheral injections of morphine or the morphine-potentiating agents CCK(1) (lorglumide) and the CCK(2) (LY-225910) receptor antagonists can induce morphine sensitization. Each animal was treated with 5 daily i.p. injections of saline (control group), 1.5 mg/Kg morphine hydrochloride (group morphine), and 1.0 mg/Kg lorglumide (group LOR) or LY-225910 (group LY). One, two, three and four weeks after the last treatment day, all animals were challenged with one i.p. injection of morphine (1.5 mg/Kg). The morphine, LOR groups and group LY showed a significant increase in percentage of animals displaying STR. These data demonstrate that the blockade of endogenous CCK actions leads to morphine sensitization probably through both CCK receptors. The present data are consistent with the antagonistic effects of CCK and opioids in the control of morphine-induced STR. In addition, these results suggest that both CCK receptors are involved in the modulatory effects of CCK on this morphine effect.

Analgesics, Opioid↗

PubMed1998

Effects of haloperidol and GM1 ganglioside treatment on striatal D2 receptor binding and dopamine turnover.

Previous studies have shown that whereas exogenous GM1 ganglioside co-administration leads to an increase of haloperidol-induced behavioral supersensitivity, GM1 significantly attenuates the behavioral parameters of dopaminergic supersensitivity when administered after abrupt haloperidol withdrawal. In the present study, the effects of GM1 and haloperidol co-administration (5 mg/kg GM1 i.p. and 1 mg/kg haloperidol i.p., twice daily, for 30 days) as well as the effects of a 3 day treatment with GM1 were investigated in rats withdrawn from haloperidol administration by measuring striatal D2 dopamine receptor binding and dopamine turnover. The results showed that under these two experimental conditions GM1 modified neither the haloperidol-induced striatal D2 dopamine receptor up regulation nor the decrease in dopamine turnover produced by haloperidol withdrawal. These results suggest that the effects of GM1 on behavioral supersensitivity are not related to modifications in dopamine receptor number or affinity and in the synaptic availability of this catecholamine.

Animals↗

PubMed1997

Developmental and behavioral effects of postnatal amitraz exposure in rats.

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 +/- 2.0), 4 (12.3 +/- 1.2) and 5 (8.7 +/- 0.9) in relation to controls (10.6 +/- 1.2; 4.5 +/- 0.6 and 3.4 +/- 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 +/- 11) and 17 (124 +/- 12), and 16 (104 +/- 9), 17 (137 +/- 9) and 18 (106 +/- 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 +/- 11 and 69 +/- 10 for days 16 and 17 and 49 +/- 9, 48 +/- 7 and 56 +/- 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Animals↗

PubMed1993

Effects of amitraz on motor function.

The effects of amitraz, a formamidine derivative, on motor function were studied in rats. Behavioural and neurochemical studies were performed. Results show that amitraz was able: 1) to decrease locomotion and rearing frequencies of rats and to increase their immobility time in an open-field; 2) to displace to the left the control dose-response curve constructed to apomorphine-induced stereotyped behavior; 3) to potentiate both pentobarbital sleeping time and amphetamine effects on open-field behaviour of rats and 4) to increase not only the whole brain levels of noradrenaline but also the striatal levels of dopamine. In relation to control animals, the pesticide also induced 5) a decrease in the striatal levels of homovanillic acid, 6) pesticide effects on open-field behaviour of rats were not antagonized by yohimbine administration, and 7) metoclopramide administration on amitraz pretreated rats antagonized not only amphetamine effects on open-field behaviour, but also apomorphine-induced stereotypy. These results are discussed in the light of the actions of amitraz on biogenic amines. It is suggested that the pesticide effects on motor function are consequences of the inhibitory effects on MAO activity, most probably through the increases produced on catecholamine levels within the central nervous system.

Amines↗

PubMed1990

Effects of dihydroergotoxine on some dopamine-related behaviors in rats.

1. The effects of dihydroergotoxine on open-field behavior, apomorphine-induced stereotype and haloperidol-induced catalepsy were studied quantitatively in rats. 2. Dihydroergotoxine decreased the open-field behavior of rats, in a dose-dependent manner; this effect remained at least for 8 hr. 3. Dihydroergotoxine (10.0 mg/kg) caused a 1.40 leftward displacement of the dose-response curve constructed for apomorphine-induced stereotypy; the ED50 for apomorphine was reduced from 0.40 (+/- 0.05) to 0.29 (+/- 0.03). 4. Dihydroergotoxine (10.0 mg/kg) was unable to change haloperidol-induced catalepsy. 5. Results were discussed in the light of a possible interference of central noradrenergic systems with the expression of dopaminergic behaviors.

Animals↗

PubMed1989

Some behavioral effects of the pesticide amitraz.

Acute oral administration of the pesticide amitraz at the doses of 60 and 100 mg/kg (N = 10 per group) significantly decreased the rearing frequency of rats observed in an open field to 8 +/- 8 and 5 +/- 5, respectively, when compared to 28 +/- 5 for control rats treated with vehicle only. The same doses of amitraz (N = 10 per group) increased duration of immobility to 80 +/- 50 and 113 +/- 64 s, respectively, when compared to 113 +/- 64 s for the controls. Acute oral administration of amitraz (20, 60 or 100 mg/kg, N = 10 per group) significantly increased the convulsive threshold dose of rats for strychnine, picrotoxin and pentylenetetrazole. Amitraz administered ip to mice at the doses of 20, 60 and 100 mg/kg (N = 10 per group) significantly increased sleeping time in a dose-dependent manner to 96 +/- 26, 120 +/- 29 and 198 +/- 58 min, respectively, when compared to 45 +/- 15 min for control mice treated with vehicle only. These results indicate that amitraz produces a depressant effect on the central nervous system.

Analysis of Variance↗

PubMedDate not supplied

Developmental and behavioral effects of prenatal amitraz exposure in rats.

The effects of prenatal amitraz exposure on physical and behavioral parameters of rats were studied. Pregnant rats were orally gavaged with amitraz (20 mg/Kg) or with distilled water (1.0 ml/Kg) on Days 1, 4, 7, 10, 13, 16, and 19 of pregnancy. After birth, cross-fostering was performed thus generating the following groups: control pups nursed by control dams (CC); control pups nursed by treated dams (CE); treated pups nursed by treated dams (EE) and treated pups nursed by control dams (EC). Results show that compared to pups of Group CC, groups prenatally exposed to amitraz (EC and EE) showed decreased age of vaginal opening. Group EE also showed earlier fur development and a delay in incisor eruption compared to Group CC. The ages of pinna detachment, eye and ear opening, testes descent, and reflex development (surface righting and startle) were not affected by amitraz exposure. Offspring of group CE also showed earlier fur development. Rats of group EE had higher locomotor activity and rearing frequency and shorter immobility time compared to the rats of group CC when observed in an open-field 30 days after birth but not 60 and 90 days. No significant differences were found in open-field behaviors among the CC, CE, and EC groups. The present findings indicate that prenatal exposure to amitraz caused transient developmental and behavioral changes in the exposed rat offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human offspring may be warranted.

Animals↗