Altered pre-pulse inhibition in adult rats treated neonatally with domoic acid

Altered functioning of the glutamate system during critical periods of development is believed to play a role in various neurodevelopmental disorders, such as schizophrenia. Prepulse inhibition (PPI) of the acoustic startle response is deficient in people with schizophrenia. This study investigated the theory that neonatal treatment with domoic acid (DOM), a glutamate agonist, leads to deficient PPI. Results indicate that neonatal treatment with DOM leads to lowered PPI in adult males and an increased startle response in adult females.     

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.     

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.     

Effect of neonatal benzpyrene imprinting on the brain serotonin content and nocistatin level in adult male rats

Single neonatal treatment (imprinting) with 20 microg benzpyrene results in significant increase of the brain serotonin level in the striatum, while in the other four regions (cortex, brainstem, hippocampus, hypothalamus) when measured in adults can be detected. The nocistatin level of cerebrospinal fluid (CSF) significantly decreases, while there is no change in the plasma nocistatin level. The results call attention to the comprehensive imprinting effect of benzpyrene, which in addition to receptorial, hormonal and sexual behavioral disturbances causes lasting differences in the brain serotonin and nocistatin levels, probably influencing mood and pain tolerance.     

Prolonged effect of a single serotonin treatment in adult age on the serotonin and histamine content of white blood cells and mast cells of rats

Hormonal imprinting was provoked by serotonin treatment in adult age. Three weeks after treatment with 100 microg serotonin, the serotonin and histamine content of peritoneal cells (mast cells, lymphocytes and the monocyte-macrophage-granulocyte group), white blood cells (lymphocytes, granulocytes and monocytes) and thymic lymphocytes was studied by flow cytometry. The content of both amines was significantly higher in the mast cells of males and lower in females. Blood lymphocytes contained a higher serotonin and histamine level in males, and a lower serotonin level in females. The peritoneal monocyte-macrophage-granulocyte group contained less serotonin in both males and females. Thymocytes contained higher levels of both amines in females and higher histamine level in males. The experiments demonstrate that a single treatment at adult age can provoke imprinting, which alters-in the present case-the serotonin and histamine content of immune cells durably.     

Chromatin degradation in white blood cells of irradiated rats

A study was made of the dose-time relationship during chromatin degradation in white blood cells of non-irradiated and irradiated rats. There was a linear increase in the release of PDN from leukocytes 1,2 and 3 days after irradiation (1-3 Gy) followed by the deceleration of the chromatin degradation at doses exceeding 3 Gy.     

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.     

Effect of single neonatal or repeated benzpyrene exposure on the serotonin content of immune cells in young male rats

In earlier experiments single benzpyrene treatment of newborn rats caused strong alterations in the endorphin content of adult rats' immune cells. In the present experiments young (4-6 weeks old) male rats were studied for demonstrating the effect of the single neonatal or repeated (neonatally and at weanling) benzpyrene exposure on the serotonin content of immune cells (blood lymphocytes, monocytes, granulocytes; peritoneal fluid lymphocytes, mast cells, monocytes and granulocytes, thymic lymphocytes). Flow cytometric analysis showed that 50 microg benzpyrene treatment of five-week-old animals was ineffective after 5 days and this was the situation four weeks after single neonatal (20 microg) benzpyrene exposure. However, the repeated treatment of neonatally benzpyrene exposed 4 weeks old animals after 5 days resulted in elevated blood and thymic lymphocyte serotonin amount and in one index (peritoneal monocyte-granulocyte group) reduced serotonin content. This means that neonatal benzpyrene treatment does not influence directly the serotonin content (production or transport) of immune cells (unlike to the endorphin content) however, sensitizes them to a following benzpyrene exposure. The results widen the list of harmful effects (influencing steroid receptor binding, sexual behavior and immune cells' endorphin content) of perinatal benzpyrene exposure.     

Quantitative analysis of Sertoli cells in neonatally oestrogen-treated rats

On Day 1 of age rats were treated with 500 micrograms oestradiol benzoate. Oestrogen-treated rats had increased numbers of Sertoli cells per reference area or volume, whereas the total number of cells per testis was unchanged. The mean nuclear size was significantly smaller in oestrogen-treated rats than in control rats, at 22 and 45 days of age. The volume density of the heterochromatin clumps decreased from 22 to 45 days of age in control rats (68% fall), the decrease being slower in oestrogenized animals (30% fall) during the same period. The differences were significant at 45 days of age only. The relative volume occupied by the nuclear membrane infoldings was significantly less in oestrogenized rats than in control ones at the two ages considered. Nucleolar development was delayed in oestrogen-treated rats, which had lower numbers of nuclear sections showing nucleoli, as well as a decrease in the nucleolar diameter. We suggest that these Sertoli cell alterations are due to the altered gonadotrophin and testosterone concentrations induced by the steroid treatment rather than to a direct effect of oestrogen.     

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.     

Influence of neonatally administered gonadotropin on the sexual function of adult rats]

Male and female rats were daily injected with 10 IU HCG plus 10 IU FSH from the 1st to 14th day of life in order to investigate the influence of neonatal gonadotrophin administration on the sex-specific differentiation of the brain. When adult, the males showed hypogonadism associated with approximately normal sexual activity. In the females, precocious puberty, indicated by premature vaginal opening and spontaneous estrus, occurred. Furthermore, bisexuality with a tendency towards more male behavioural patterns was observed, but no impairment of ovarian cyclicity. Thus, hypergonadotrophic hypergonadism during the hypothalamic differentiation phase gave rise to bisexual behaviour in adult female rats associated with normal ovarian cycles. The question of a direct or indirect influence of gonadotrophins on the sex-specific brain differentiation is discussed.