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Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Environmental information received by a mother can induce a phenotype change in her offspring, commonly known as a maternal effect (trans-generational effect). The present work verified the effects of lipopolysaccharide (LPS), which mimics bacterial infection, on maternal care and on the activity of related brain areas in F1 offspring, i.e., female rats that were prenatally exposed to LPS., Main Methods: Pregnant rats received 100μg/kg of LPS intraperitoneally on gestational day (GD) 9.5. Female offspring of the F1 generation were mated to naïve males and were evaluated during their lactation period for open field, maternal and aggressive behaviors. Striatal and hypothalamic dopamine and serotonin levels and turnover were also evaluated. Furthermore, astrocyte protein expression in the nucleus accumbens (NA) was analyzed in F1 females to assess LPS-induced neuroinflammation., Key Findings: Prenatal LPS did not change open field behavior but impaired both maternal and maternal aggressive behaviors in the F1 generation. LPS exposure also reduced both striatal levels of dopamine and serotonin and its metabolites, but induced no changes in NA astrocyte expression., Significance: We suggested that the observed impairments in the F1 females were a consequence of a motivational change induced by prenatal LPS, as (1) no changes in motor activity were observed, (2) prenatal LPS-exposure was reported by our group to induce motivational impairments in males, and (3) the existence of a strong connection between striatal dopaminergic activity and motivation-oriented activities. The present findings strongly indicate a maternal effect for prenatal LPS, at least for the F1 generation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system., Materials and Methods: The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT(1A) receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment., Results: The present work found anxiolytic-like activity of the EO at the dose of 10mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LDB, indicating that the EO activity occurs via the GABA(A) receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus., Conclusions: The results corroborate the use of Cymbopogon citratus in folk medicine and suggest that the anxiolytic-like effect of its EO is mediated by the GABA(A) receptor-benzodiazepine complex., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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.

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.

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.

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.