Age-dependent DOCA-salt hypertension in Brattleboro rats: the role of vasopressin

The age-dependent participation of endogenous vasopressin (VP) during the development of DOCA-salt hypertension was studied in young (28-day-old) and adult (75-day-old) Brattleboro rats. VP-deficient homozygous (DI) rats were compared to heterozygous (non-DI) littermates which do synthetize VP. Six weeks of DOCA-salt treatment did not increase blood pressure (BP) in adult DI rats. On the other hand, in young DI animals there was a significant rise of systolic and mean arterial pressure accompanied by the hypertrophy of the left ventricle. This moderate DOCA-salt hypertension of young DI rats contrasted with severe hypertension of young non-DI rats. Increased BP response of young VP-deficient DOCA-salt treated rats was independent of the saline intake or blood volume expansion which were similar in young hypertensive and adult normotensive DI animals. It could be concluded that vasopressin is not essential for the induction of DOCA-salt hypertension in young rats even if VP is responsible for the magnitude of BP elevation. In contrast to young animals vasopressin is very important for the development of DOCA-salt hypertension in adult rats.     

The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats

Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which—among other things—include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine-induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine-tuning of GABAergic and serotonergic function.     

Effect of vasopressin on open field and activity behavior of the vasopressin-deficient (Brattleboro) rat

The effect of 1 and 5 micrograms AVP injections on open field and photoactivity chamber behavior of D.I. and normal Long-Evans animals was studied. Administration of 5 micrograms AVP (SC) resulted in a statistically significant depression of both open field and photochamber activity in the D.I. rat, but had a less pronounced effect on normal animals. However, 1 microgram AVP resulted in only minor alterations of activity in both D.I. and normal animals. In terms of learned behavior, D.I. and normal animals displayed similar within-session habituation when comparisons were made following the same treatment conditions. Thus, this study supports the hypothesis that vasopressin may influence memory tasks by modulation of related states of emotionality, motivation, and/or attention rather than by direct involvement in the retrieval and/or consolidation of information.     

Effects of prolactin deficiency during the early postnatal period on the development of maternal behavior in female rats: Mother's milk makes the difference

During early life, prolactin (PRL) ingested by the pups through the milk participates in the development of neuroendocrine, immunological and reproductive systems. The present study tested whether a deficiency in PRL in the dam's milk during early lactation affected the offspring in terms of the maternal responsiveness in the sensitization paradigm and behavioral response to a novel environment in the offspring. Thus, lactating rats were injected (sc) on postnatal days (PND) 2–5 with bromocriptine (125 μg/day), bromocriptine + ovine PRL (125 μg + 300 μg/day), or vehicle. As juveniles (at PND 24) or adults (PND 90–100), one female from each litter was exposed to 5 foster pups continuously for 8 days and their maternal responsiveness was recorded. Female offspring were also tested in an open field arena. Adult, but not juvenile, female offspring of bromocriptine-treated mothers showed an increased latency to become maternal, in comparison to latencies displayed by the offspring of control mothers. Furthermore, the proportion of adult, but not juvenile, offspring of bromocriptine-treated mothers that became maternal was lower than that showed by the offspring of vehicle-treated mothers. In comparison to female offspring of vehicle-treated mothers, female offspring of bromocriptine-treated mothers spent less time hovering over the pups (as juvenile females), body licking (as both juvenile and adult females), and in close proximity to pups (as adult females) during the maternal behavior test. Simultaneous administration of ovine PRL and bromocriptine reversed almost all the negative effects of bromocriptine. These data suggest that maternally-derived PRL participates during the early postnatal period in the development of neural systems that underlie the control of maternal behavior.     

Changes in susceptibility to bacterial endotoxin and infection during the early postnatal period in rats

1. (1)
   На крысятах различного возраста (1, 5, 10 и 15-днeвных) тeстировали токсичность инактивированного штамма Salmonella paratyphi B. B тeчeниe пeрвых 2 вeдeль жизни чувствитeльность крыс044F;т к эндотоксичeскому дeйствию этого микроба повышаeтся приблизитeльно в 7 раз. Это повышeнная чувствитeльность сохраняeтся и во взрослом состоянии.     
   
   

Effects of change of maternal environment during early postnatal development on behaviour in cataleptic rats

Pinch-induced catalepsy was compared at an age of 2 weeks and at weaning in cataleptic GC and control Wistar rats reared by their biological mothers or subjected to reciprocal in-or cross-fostering. Besides, some open-field parameters were studied in the same groups of rats at an age of 2 months. Significant interstrain differences in all the behavioural parameters studied were found. Reciprocal cross-fostering tended to diminish interstrain differences in most parameters. It brought about a decrease of duration of pinch-induced catalepsy at 2 weeks and at weaning in GC rats, and an increase of duration of catalepsy at weaning in Wistar females. Besides, cross-fostering decreased the duration of freezing in the open-field test in GC rats at 2 months.     

Deficiency of the paternally inherited gene Magel2 alters the development of separation-induced vocalization and maternal behavior in mice

The behavior of offspring results from the combined expression of maternal and paternal genes. Genomic imprinting silences some genes in a parent-of-origin specific manner, a process that, among all animals, occurs only in mammals. How genomic imprinting affects the behavior of mammalian offspring, however, remains poorly understood. Here, we studied how the loss of the paternally inherited gene Magel2 in mouse pups affects the emission of separation-induced ultrasonic vocalizations (USV). Using quantitative analysis of more than 1000 USVs, we characterized the rate of vocalizations as well as their spectral features from postnatal days 6–12 (P6–P12), a critical phase of mouse development that covers the peak of vocal behavior in pups. Our analyses show that Magel2 deficient offspring emit separation-induced vocalizations at lower rates and with altered spectral features mainly at P8. We also show that dams display altered behavior towards their own Magel2 deficient offspring at this age. In a test to compare the retrieval of two pups, dams retrieve wildtype control pups first and faster than Magel2 deficient offspring. These results suggest that the loss of Magel2 impairs the expression of separation-induced vocalization in pups as well as maternal behavior at a specific age of postnatal development, both of which support the pups' growth and development.     

Signs of attenuated depression-like behavior in vasopressin deficient Brattleboro rats

Vasopressin, a peptide hormone functioning also as a neurotransmitter, neuromodulator and regulator of the stress response is considered to be one of the factors related to the development and course of depression. In the present study, we have tested the hypothesis that congenital deficit of vasopressin in Brattleboro rats leads to attenuated depression-like behavior in tests modeling different symptoms of depression. In addition, hypothalamic-pituitary-adrenocortical axis activity was investigated. Vasopressin deficient rats showed signs of attenuated depression-like behavior in forced swimming and sucrose preference tests, while their behavior on elevated plus maze was unchanged. Vasopressin deficiency had no influence on basal levels of ACTH and corticosterone and had only mild impact on hormonal activation in response to forced swimming and plus-maze exposure. However, vasopressin deficient animals showed higher level of dexamethasone induced suppression of corticosterone response to restraint stress and higher basal levels of corticotropin-releasing hormone mRNA in the hypothalamic paraventricular nucleus. In conclusion, present data obtained in vasopressin deficient rats show that vasopressin is involved in the development of depression-like behavior, in particular of the coping style and anhedonia. Moreover, behavioral and endocrine responses were found to be dissociated. We suggest that brain vasopressinergic circuits distinct from those regulating the HPA axis are involved in generating depression-like behavior.     

Thermoregulation characteristics of rats exposed to cold in the early postnatal period

Cold adaptation of adult rats (at 4-5 degrees C for 7 weeks) increased their ability to respond to noradrenaline by the rise of body temperature and heat radiation, led to an almost 2-fold increase in the relative brown fat mass (BFM). Adult rats which experienced "cold imprinting" (from the first to the seventh day after birth, 15 min at 4-5 degrees C) showed a far less increment of the BFM on cold adaptation, no additional rise of body temperature and heat radiation in response to noradrenaline. In cold-imprinted rats, the relative surface of the tail and the body surface heat radiation transfer conefficient were found to be reduced. This attests to stable adaptive changes in physical thermoregulation, directed toward increase in animals' heat insulation.     

Adrenergic mechanisms regulating the motor reactions of rats in the early postnatal period

In 12-day-old rats, L-DOPA, a precursor of catecholamine synthesis, provokes an increase in the rate of the motor reactions (MR) of the shudder type. Reserpine which promotes catecholamine release from the tissues, leads to the diminution of the rate of the MR of the shudder type in rats of the same age. Aminazine, an alpha-adrenoblocker and antagonist of dopamine receptors, decreases the rate of the MR of the shudder type. Administration of aminazine in a dose of 10 mg/kg at different age periods produces inconclusive changes in the diminution of the rate of the MR of the shudder type. During sudden changes in the growth, the rate of the above-described modulations substantially decreases. The high rate of the MR of the shudder type seen in rats in the early postnatal period is a consequence of the marked activity of the catecholaminergic (dopaminergic) systems during that period. Reduction in the effect of the decreased MR rate produced by the same dose of aminazine during the critical periods of the growth also attests to the high activity of the catecholaminergic (dopaminergic) system in rats at that period.     

Ultrasonic vocalization in rat pups: effects of early postnatal exposure to haloperidol

The effects of prolonged postnatal administration of haloperidol (H) on ultrasonic vocalization elicited by the removal of rat pups from their nest were investigated. The results show that the number of ultrasonic calls was significantly reduced by H exposure from the 8th until the 14th day after birth. Conversely, this neuroleptic significantly increased the duration of ultrasound from the 4th up to the 16th day of age. Moreover, changes in the frequency of calls were produced by early postnatal treatment with H. These alterations could be due to an impaired functional maturation of the dopaminergic system produced by neonatal exposure to H. Furthermore, the present data suggest that ultrasonic vocalization may be considered as an early sensitive indicator of subtle changes elicited by the postnatal treatment with a dopamine receptor blocking agent at dose levels below those associated with overt signs of neurotoxicity.     

Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats

We asked whether cyclooxygenase (COX) activity controls the renin-angiotensin system in the postnatal period. During kidney development, renin peaked at postnatal days 0-1 at the mRNA, tissue protein [renal renin concentration (RRC)], and plasma renin concentration (PRC) levels and was widely expressed along preglomerular vessels. PRC and renin mRNA expression was elevated until weaning in the 4th postnatal week compared with adult rats. Renocortical COX-2 was restricted to Tamm-Horsfall protein-positive cells in the thick ascending limb of Henle's loop, and cortical COX-2 mRNA and protein expression were elevated along with PRC in the 2nd and 3rd postnatal weeks. In contrast, cortical COX-1 expression was constant, but medullary COX-1 expression increased eightfold from the 1st to 4th postnatal week. A COX-2-selective blocker, parecoxib, and a nonselective blocker, indomethacin, given in a period with COX-2 induction from postnatal day 6 to day 12, markedly decreased PRC, but not renin mRNA or RRC. Inhibition of angiotensin AT(1) receptors by candesartan from postnatal day 1 to day 5 increased COX-2 mRNA (2.5-fold), protein, and distribution, renin mRNA (7-fold) and PRC (20- to 70-fold), but had no influence on COX-1 mRNA. Thus, due to very low levels of expression, COX-2 is unlikely to be responsible for the birth peak of renin, but COX-2 activity supports renin secretion later in the suckling period. ANG II negatively feeds back on renocortical COX-2 expression in the 1st postnatal days with high activity of the renin system. We suggest that suckling in the rat is correlated to an enhanced, COX-2-mediated, secretory activity of renin-producing juxtaglomerular cells.     

Ontogenetic and lung development in Tupaia belangeri during the early postnatal period

The Belanger's tree shrew (Tupaia belangeri) has an unusual reproductive strategy. The animals are born in altricial condition and remain in the nest for the first four weeks of life, nursed only once in 48 h. This is highly demanding for the constitution of the neonates. Despite their immaturity in the external appearance at birth, newborn tree shrews have to deal with the absence of the mother. We asked if the lung structure of the neonates match the high physiological requirements of this “absentee system”. To examine the lung development of nest young tree shrews, histological and ultrastructural investigations were performed. Newborn tree shrews are at the transition stage between the saccular and the alveolar stage of lung development. In addition to small saccules, the lung has alveoli and associated structures already at birth and thus appears more mature compared with typical altricial species. The results of the present study reveal that despite their immaturity in the external appearance newborn tree shrews are relatively mature in terms of lung development. This can be interpreted as a prerequisite for thermoregulatory abilities, necessary in neonate tree shrews to cope with the restricted nature of maternal care.