Ensaios preliminares em ratas wistar com extrato hidroetanólico de calunga (Simaba ferruginea St. Hil. ) v. o., nas fases gestacionais de implantação, organogênese e período fetal: interferências na prole / Preliminary trials on female Wistar rats with hydroethanolic extract from "calunga" (Simaba ferruginea St. Hil. ) in the gestational stages of implantation, organogenesis and fetal period: interference on offspring

RESUMO A susceptibilidade dos conceptos a agentes químicos varia muito em cada estágio do desenvolvimento. Devido a isto, a maioria dos países passou a exigir a análise do potencial para afetar todos os aspectos da reprodução (espermatogênese, acasalamento, prenhez, parto e lactação) para o desenvolvimento de novos medicamentos e fitoterápicos. O presente trabalho objetivou avaliar o efeito do extrato hidroetanólico de Simaba ferruginea St. Hil (calunga) (EHSF) v.o., em ratas da linhagem Wistar tratadas durante a prenhez e verificar a interferência no desenvolvimento intra-uterino da prole. As ratas foram tratadas com EHSF 50 e 100 mg Kg-1 ou água destilada, do seguinte modo: a) do 1º ao 6º dia de prenhez (período da formação do blastocisto e implantação); b) do 8º ao 16º dia de prenhez (fase embrionária de organogênese); c) do 15º ao 19º dia de prenhez (fase do desenvolvimento fetal). O tratamento do 1º ao 6º dia, mostrou redução no número de fetos com ambas doses e não alterou o peso do útero / ovário nem peso corporal das mães. Quando as ratas foram tratadas na fase da organogênese verificou-se, redução estatisticamente significante do número de fetos vivos com a dose 50 mg Kg-1, e o aparecimento de fetos mortos em 30% das fêmeas tratadas com EHSF 50 mg Kg-1 e em 20% nas fêmeas tratadas com a dose de 100 mg Kg-1, não houve alteração no peso do útero / ovário nem no peso corporal das matrizes. Finalmente, o tratamento no período fetal não afetou o número de filhotes vivos, não provocou malformações anatômicas visíveis a olho nu, nem reabsorção fetal; porém, observou-se que 10% das mães tratadas com 50 mg Kg-1 apresentaram 2 fetos mortos e 20% das mães tratadas com 100 mg Kg-1 apresentaram, em média, 4 fetos mortos. Com estes dados, pode ser concluído que o EHSF apresenta baixa ou nenhuma toxicidade materna para ratas Wistar, embora seja letal para alguns descendentes, independente da fase da prenhez em que foram realizados os tratamentos ...

ABSTRACT The susceptibility of concepts to chemical agents varies a lot at each development stage. Because of that, most countries started requiring the analysis of potential to affect all aspects of reproduction (spermatogenesis, mating, pregnancy, birth and lactation) for the development of new drugs and herbal medicines. This study aimed to evaluate the effect of the hydroethanolic extract of Simaba ferruginea St. Hil ("calunga") (EHSF) on female Wistar rats treated during pregnancy in order to check the interference on the intrauterine development of the offspring. The rats were treated with EHSF 50 and 100 mg/kg-1or distilled water, as follows: a) from day 1 to day 6 of pregnancy (period of blastocytes formation and implantation); b) from day 8 to day 16 of pregnancy (embryonic phase of organogenesis); c) from day 15 to day 19 of pregnancy (fetal development phase). The treatment from day 1 to day 6 showed reduction on the amount of fetuses with both doses and it did not alter neither the weight of the uterus / ovary nor the body weight of the mothers. When the female rats were treated in the organogenesis phase, it was verified both statistical significant decrease on the number of live fetuses for the 50 mg / Kg-1, and also appearance of dead fetuses in 30% of the female rats treated with EHSF 50 mg / Kg-1. In 20% of the female rats treated with 100 mg / Kg-1, there was no alteration neither in the weight of the uterus / ovary or in the body weight of the matrixes. Finally, the treatment in the fetal period did not affect the number of live descendants, or caused anatomical malformations visible to naked eye and fetal reabsorption. However, 10% of the mothers treated with 50 mg / Kg-1presented 2 dead fetuses and 20% of the mothers who had 100 mg / Kg-1showed, on average, 4 dead fetuses. With this data, we can conclude that EHSF presents low maternal toxicity for Wistar rats, although being fatal to some descendants, not mattering in which pregnancy phase the treatments have been performed, being more evident in the earlier phases. For this reason, it is recommended to avoid the use of this plant in pregnancy case.

Prolactin induces adrenal hypertrophy

Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin) also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc). In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05), and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05). We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 æm² for treated and control animals, respectively; P < 0.05), and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 æm²; P < 0.05). Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant

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 ñ 1.5 vs 17.4 ñ 2.3) in the open arms as well as a tendency to a reduction in percent entries into the open arms (35.7 ñ 4.7 vs 45.7 ñ 4.3). These results show that the physiological state of lactation modulates the open-field and EPM behaviors in rats.

Is perinatal picrotoxin anxiogenic?

Female Wistar rats were exposed to a subconvulsant dose of picrotoxin (0.75 mg/Kg,sc) on day 18 of pregnancy, immediately after paturition and daily during the first 5 days of lactation. In adulthood, the offspring were tested in an open-field, in an elevated plus maze and for social interaction. Results showed increased locomotor activity (75 days of age) and decreased social interaction (90 days of age) in experimental male rats compared to control male rats. No effects on behaviors related to anxiety were observed in males or females tested in the plus maze apparatus. An additional comparison of the activity male animals perinatally treated with picrotoxin showed a lack of the classical sexual dimorphic responses in the open-field (control male = 68.7 ñ 6.31; control female = 98.4 ñ 6.31; edxperimental male = 89.6 ñ 6.32; experimental female = 113.2 ñ 4.74). We suggest that perinatal picrotoxin exposure may interfere with normal male masculinization rather increasing anxiety in male rats

Intracerebroventricular administration of cholecystokinin reduces stereotypy in dopamine supersensitive rats

Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 µl) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icvand long-term saline-treated rats that received CCK-8(SCCK,N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 + or - 1.7 vs 31 + or - 1.6; P<0.05) and CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8

Effects of chronic domperidone treatment on rat conditioned avoidance behavior

The effects of chronic administration of domperidone (DOM), a peripherally acting anti-emetic and hyperprolactinemic D2-dopaminoceptor antagonisti, on active and inhibitory conditioned behavior were tested on male and female rats. DOM (4 mg/Kg) was injected ip daily either for 5 or 30 days. Although treatment for 5 days failed to effect experimental parameters, treatment for 30 days impaired the performance of active conditioned avoidance of female, but not male, rats. This effect was no longer observed 7 days after ending treatment. No effects of DOM treatment were observed on active conditioned avoidance of male rats or on inhibitory conditioned behavior of all rats. These data suggest that female rats are more susceptible to the hyperprolactinemic effects of DOM than male rats. However, an influence of estrous cycle interruption cannot be rejected

Effect of acute bromopride treatment on rat prolactin levels and sexual behavior

Acute intraperitoneal adminsitration of bromoprid (BRO), a dopamine D2 blocker used as an anti-emetic drug in gastroenterology was tested in male and female ratas for its effect on prolactin (PRL) serum levels and on sexual behavior. Rats that received 2.5 mg/Kg BRO, the lowest dose tested, showed a maximal nincrease in PRL serum levels. Male rats that received 5.0 mg/Kg BRO showed higher postejaculatory mount lactency and postejaculatory intromission latency than controls. Rats treated with 10.0 mg/Kg BRO showed higher mount latency, intromission latency, ejaculation latency, postejaculatory mount latency and a lower percentage of animals showing mount and ejaculation. Female rats that received 5.0 mg/Kg BRO showed a lower lordosis quotient. The data suggest that glockade of postynaptic dopamine D2 receptors inhibitis male and female sexual behavior and that this inhibition is not related solely to the increase in PRL lelvels

Acute bromopride treatments: effects on general activity and inhibitory avoidance in rats

Bromopride (BRO), a dopamine D2 blocker used in gastroenterology clinics, was tested acutely in rats for effects on general activity, measured in an open-field test, and on inhibitory avoidance behavior. Rats that received 2.5 and 5.0 mg/Kg BRO showed lower locomotion and rearing frequencies than controls, and 5.0 mg/Kg BRO blocked the inhibitory avoidance response. The data suggest that BRO may have neuroleptic effects