Effect of nitric oxide inhibition on blood pressure and corticosterone responses in adult rats neonatally treated with glutamate

The role of nitric oxide (NO) in the regulation of blood pressure and hypothalamic-pituitary-adrenal function of adult rats treated with monosodium glutamate (MSG) during the neonatal period was investigated. Blood pressure and the heart rate were registered by a computerized system of direct blood pressure measurement through an indwelling cannula in the femoral artery. The inhibition of the activity of NO synthase by acute injection of Nomega-nitro-L-argininemethylester (L-NAME, 30 mg/kg, i.v.) to control rats produced a rise of blood pressure and a fall of heart rate. Both responses were reduced in MSG-treated rats. Repeated administration of L-NAME (50 mg/kg, i.p, two times daily for 4 days) increased BP in both groups of animals. Corticosterone concentrations in the plasma were significantly increased in response to repeated L-NAME administration in MSG-treated rats, while ACTH levels were similar in both groups of animals. These data suggest that some of the cardiovascular and endocrine changes in rats treated with MSG may be due to the abnormal function of the NO system.     

Pituitaries of rats neonatally treated with oestrogen

Summary Pituitaries of male and female rats neonatally treated with oestradiol dipropionate were examined with light and electron microscopy, disc electrophoresis and in vitro C¹⁴-leucine incorporation.Single dose of oestradiol administered shortly after birth to male rats has an prolonged stimulative effect on LTH synthesis and release. This is expressed in the cell hypertrophy, proliferation of ER, increase of corresponding band density and higher rate of ¹⁴C-leucine incorporation. In females this effect was less pronounced.STH cell in the treated male pituitaries were degranulated, corresponding hormone band density significantly lowered and incorporation of ¹⁴C-leucine was reduced. This could be considered as an inhibitory effect of oestradiol on STH synthesis and release. Such effect was more expressed two than four months after treatment and is more pronounced in male than in female rats.The technical assistence of Slobodanka Selimovi is gratefully acknowledged.     

Sex-differentiated enzyme levels and oestrogen uptake in adult rats treated neonatally with tamoxifen or CI-628

Serum cholinesterase, hepatic histidase and monoamine oxidase activity levels are higher in adult female rats than in adult male rats. Exposure of neonatal rats to antioestrogen (tamoxifen or CI-628) resulted in increased serum cholinesterase in adult females only and no effect on hepatic histidase and monoamine oxidase in both sexes. Neonatal tamoxifen or CI-628 treatment resulted in reduced body weights in adult male rats and reduced uterine wet weights in adult female rats. Circulating oestrogen levels measured in adult female rats treated neonatally with tamoxifen were not significantly different from controls. Specific oestrogen uptake in the brain of adult male and female rats was found to be higher in the pituitary than in the preoptic-anterior hypothalamic area and the median eminence-basal hypothalamus than in the cerebral cortex. There was higher uptake of [3H]oestradiol-17 beta in male pituitaries than in female pituitaries. No other sex-difference was observed. Neonatal tamoxifen treatment did not alter the capacity of these brain tissues to take up oestrogen. It is suggested that neonatal antioestrogen exposure has altered the endocrine expression of serum cholinesterase in adult female rats by interfering with normal imprinting mechanisms.     

Endorphin content of white blood cells and peritoneal cells in neonatally benzpyrene treated adult rats

White blood cells of rats (lymphocytes, monocytes, macrophages, granulocytes and mast cells) contain beta-endorphin. Two months after a single neonatal benzpyrene treatment (imprinting) there is an elevated level of immunoreactive endorphin in the blood and peritoneal cells of female animals and blood cells of males. The endorphin content decreased in the peritoneal cells of males. In the blood, the granulocytes of female, and the lymphocytes of male rats contained the highest amount of endorphin. In the peritoneal fluid also the granulocytes of females contained the highest amount of endorphin, in contrast to males, where the endorphin content of cells decreased and the lowest level of it was present in the lymphocytes. The experiments justify that benzpyrene treatment can durably influence endorphin levels of white blood cells and gives new data to the already known lifelong health destroying effects of perinatal benzpyrene exposition (alterations of hormone receptor binding capacity and sexual behavior).     

Potentiation of vasopressin analgesia in rats treated neonatally with monosodium glutamate

The analgesic response elicited by central administration of arginine vasopressin (AVP) appears to be dependent upon the integrity of the hypothalamic paraventricular nucleus (PVN), since lesions placed in the PVN eliminate AVP analgesia. A projection to the zona externa of the median eminence constitutes one of the VP-containing efferents of the PVN. Neonatal treatment with monosodium glutamate (MSG) destroys perikarya of the arcuate nucleus and median eminence. The present study examined whether AVP analgesia was affected in the MSG-treated rat and whether these alterations were accompanied by specific changes in VP immunoreactivity in the zona externa of the median eminence. Female rats, neonatally treated with either MSG or a saline control, were tested as adults on the tail-flick test following intracerebroventricular injections of 0, 75, 150 and 500 ng doses of AVP. After testing, selected animals were prepared for AVP and oxytocin immunocytochemistry of the median eminence. Significant potentiations in the magnitude of AVP analgesia were observed in MSG-treated rats. AVP and oxytocin immunoreactivity in the zona interna and oxytocin immunoreactivity in the zona externa of the median eminence were similar in MSG-treated and control rats. In contrast, AVP immunoreactivity in the zona externa of the median eminence was markedly reduced in the MSG-treated rat. These data suggest that VP analgesia may normally be inhibited by those medial-basal hypothalamic neurons affected by neonatal MSG treatment.     

Plasma testosterone levels and ovarian testosterone content in adult mice treated with diethylstilbestrol neonatally

Neonatal female NMRI mice (n = 16) were treated with 5 micrograms diethylstilbestrol (DES) per day, for the first 5 days after birth and killed postpubertally. Control females (n = 52) were injected with vehicle only and killed in different stages of the estrous cycle. The plasma testosterone level was significantly lower in DES females than in control females in any of the estrous phases. Ovariectomy (n = 5), adrenalectomy (n = 5) or a combination of both ablations (n = 3) did not affect the plasma testosterone in DES treated females while it was significantly reduced in control females (ovariectomy n = 5; adrenalectomy n = 9); most effective was the combination ovariectomy-adrenalectomy (n = 7). Ovarian homogenates from DES treated females (n = 10) had a significantly lower testosterone content than homogenates from control females in any phase of the estrous cycle (6-10 females per phase), which held true on both a per ovary basis and when related to ovarian weight. After a 2 h incubation in vitro, the testosterone levels had increased significantly in DES homogenates (n = 6) and to a lower extent in homogenates from control females in estrus (n = 9). No similar effect was found in homogenates from diestrus (n = 10) or proestrus (n = 9) females. The results are discussed in relation to the special ovarian morphology of adult but neonatally DES treated females and also with respect to endocrine control mechanisms.     

Chronic treatment with estradiol restores depressive-like behaviors in female Wistar rats treated neonatally with clomipramine

Neonatal administration of clomipramine (CMI) induces diverse behavioral and neurochemical alterations in adult male rats that resemble major depression disorder. However, the possible behavioral alterations in adult female rats subjected to neonatal treatment with clomipramine are unknown. Therefore, the aim of this study was to explore the effect of neonatal treatment with CMI on adult female rats in relation to locomotion and behavioral despair during the estrus cycle. Also evaluated was the effect of chronic treatment with E2 on these female CMI rats. We found no effects on spontaneous locomotor activity due to neonatal treatment with CMI, or after 21 days of E2 administration. In the FST, neonatal treatment with CMI increased immobility and decreased active swimming and climbing behaviors. Influence of the ovarian cycle was detected only in relation to climbing behavior, as the rats in the MD phase displayed less climbing activity. Chronic E2 administration decreased immobility but increased only swimming in CMI rats. These results suggest that neonatal treatment with CMI induces despair-like behavior in female rats, but that chronic E2 administration generates antidepressant-like behavior by decreasing immobility and increasing swimming, perhaps through interaction with the serotonergic system.     

Fluid regulation and reproductive cyclicity in female rats treated neonatally with testosterone and methandrostenolone

Female rats injected with 1 mg of testosterone propionate on day 5 after birth weighed significantly more during the immediate postpubertal period than methandrostenolone-treated (1 mg) or vehicle-injected control females. There were no differences between groups in 24-hour intakes of food or water, when expressed on a per unit body weight basis. Testosterone- and methandrostenolone-treated rats ingested less water than controls in response to acute extracellular dehydration but not after cellular dehydration. The volume of the 'sexually dimorphic nucleus' of the preoptic area was significantly greater in brains taken from the two steroid-injected groups compared to control females. Testosterone had a stronger androgenic effect than methandrostenolone in terms of disrupting the estrous cycle.     

Reproductive tract lesions in male mice treated neonatally with tamoxifen

Male mice of the NMRI/Tg strain were treated with tamoxifen for the first 3 days after birth. The affected mice were sterile, with multiple reproductive tract lesions. These lesions included testicular hypoplasia, intraabdominal testes, epididymal cysts, and squamous metaplasia of accessory glands.     

Sexual behavior and penile reflexes of neonatally castrated male rats treated in infancy with estrogen and dihydrotestosterone

Male rats castrated neonatally and treated with a combination of 0.5 μg estradiol benzoate (EB) plus 50μg dihydrotestosterone propionate (DHTP) for the next 14 days displayed normal sexual behavior when injected with testosterone propionate (TP) in adulthood. Neither EB nor DHTP alone had this developmental effect inasmuch as only 20–25% of the neonatal castrates treated with just 0.1, 0.5, or 10 μg EB, or 50 μg DHTP, displayed ejaculatory responses. The periodic application of mildly painful electric shock, which has been previously shown to markedly facilitate ejaculatory responding in normal male rats, failed to improve sexual performance in these latter subjects. This was true even of the castrates treated neonatally with DHTP which frequently intromitted. Castrates treated with EB or DHTP alone neonatally were subjected to spinal transection (after testing of sexual behavior) for examination of penile reflexes. Those treated with DHTP showed normal reflexes, characterized by numerous erections and flips, indicating the presumably nonaromatizable DHTP has developmental effects on penile reflexes similar to those of testosterone. Subjects treated with EB, including four animals that had ejaculated at least once, displayed very few, if any, erections on reflex tests and no flips. These results show that sometimes intromissive and ejaculatory patterns can occur even though the animal appears to have little or no capacity for penile reflexes.     

NMDA receptor involvement in the effects of low dose domoic acid in neonatal rats

Summary. We have previously reported that neonatal rats display enhanced sensitivity to domoic acid relative to adults, and that perinatal injections of low doses of domoic acid alter early associational learning in the newborn rat. The current study was designed to further investigate the effects of low dose domoic acid on neonatal odour conditioning and to determine if the observed effects are due in part to an action on NMDA receptors. Groups of rat pups were conditioned to a novel odour on postnatal day (PND) 8, injected with 20g/kg domoic acid either alone, or in combination with the NMDA antagonist CPP (or appropriate controls), daily from day 8–14, reexposed to the conditioning odour or a novel odour on day 9, and tested for odour preference on day 13 using a standard 3-choice paradigm. Results indicated that rats treated with domoic acid spent significantly more time over the conditioning odour than did saline-treated rats when tested on PND 13. This effect was antagonized by concomitant injection of CPP, indicating an involvement of NMDA receptors in the actions of DOM in this paradigm. Rats injected with either saline or CPP alone showed the opposite effect, i.e. a preference for the alternate odour. The results indicate that a very low dose of DOM produces a conditioned odour preference in neonatal rats and that this effect is due in part to NMDA receptor involvement, thereby emphasizing a role for both kainate and NMDA glutamate receptors in implicit memory.