Perinatal exposure to a high NaCl diet increases the NaCl intake of adult rats

To determine the effect of differences in perinatal NaCl exposure on NaCl intake, adult Sprague-Dawley female rats were maintained on diets containing either 0.12, 1.0, or 3% NaCl throughout pregnancy and lactation. The offspring were continued on the these same diets to 30 days postpartum. Thereafter, all offspring were fed the same basal diet containing 1% NaCl. At 90 days of age, the adult offspring were placed in metabolism cages for 7 days and fed 1% NaCl chow for days 1-2, and 0% NaCl chow for days 3-7. On days 6-7, the animals were free to consume both water and 0.3 M NaCl. When dietary NaCl was available, adult rats exposed perinatally to the high NaCl diet excreted significantly more sodium on days 1-2 and 6-7 than did the rats exposed to either the mid or low NaCl diets. There were no differences in sodium excretion during sodium deprivation on days 3-5. The 0.3 M NaCl intake of the high NaCl-exposed rats was also significantly greater than the intake of the mid and low NaCl-exposed rats. In another group of adult rats, exposed perinatally to either a low or high NaCl diet, the spontaneous 24-hr intake of water and 0.3 M NaCl was measured after repeated episodes of acute sodium depletion. Sodium depletion was induced by 48 hr of dietary sodium deprivation combined with a single subcutaneous injection of 5 mg furosemide. Acute sodium depletion was found to augment existing differences in NaCl intake between low and high NaCl-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rearing on basal or high dietary NaCl modifies chorda tympani nerve responses in rats

Two experiments were conducted to determine the influence of dietary NaCl level on the integrated responses of the chorda tympani (CT) nerve to salt stimulation alone and mixed with the sodium-channel blocker, amiloride hydrochloride. Five groups of adult male rats were reared on regular chow containing either basal 0.1%, intermediate 1.0%, or high 3.0% NaCl from conception to postnatal day (PD) 30 or from conception to adulthood. Adult rats reared from conception to adulthood on basal dietary NaCl demonstrated a reduction in the CT nerve response to NaCl due to a decrease in the amiloride sensitive transduction mechanism. However, the CT nerve responses of adult rats reared on basal dietary NaCl to PD30 and then switched to intermediate dietary NaCl were similar to those of rats reared for a lifetime on intermediate dietary NaCl. Similarly, the CT nerve responses to NaCl in animals reared on high dietary NaCl from conception to PD30 and then switched to an intermediate NaCl diet were comparable to animals reared on intermediate and basal dietary NaCl. However, we found that exposure to high dietary NaCl led to a greater amiloride inhibition of NaCl responses. Thus, there is critical association between dietary NaCl level over two different exposure periods and CT nerve responsiveness to NaCl specifically regarding the degree of amiloride inhibition.     

High dietary NaCl early in development enhances mean arterial pressure of adult rats

We investigated the long-term influence of early dietary NaCl on adult mean arterial pressure (MAP) and heart rate (HR), assessed continuously for 7 weeks when fed water and chow containing 1% NaCl (weeks 1, 4, 7), 0% NaCl (weeks 2-3), and 3% NaCl (weeks 5-6) while on a 12:12 light/dark cycle. Subjects were offspring of female Sprague-Dawley rats fed solid chow consisting of either 0.1% (basal), 1% (intermediate), or 3% (high) NaCl throughout pregnancy and lactation. After weaning on postnatal day (PD) 21, offspring were fed the same NaCl diet of their mother until PD 30, at which time all offspring were given Purina 5001 diet (1% NaCl) as their solid chow. On PD 60, 22 adult male offspring (eight basals, six intermediates, eight highs) were implanted with an aortic electronic sensor for transmitting blood-pressure signals by telemetry. MAP and HR varied significantly across the 7-week testing period in association with dietary NaCl levels. The three perinatal salt groups had similar HR levels on normal 1% NaCl chow. However, HR increased in all groups during 0% NaCl and decreased in all groups during 3% NaCl. In contrast, the average MAP levels were significantly greater in the highs compared to both the intermediate and basal groups during both dark and light periods. MAP increased in high and basal groups during both 0% and 3%; however, the increase was more pronounced in the highs. In conclusion, exposure to high levels of dietary NaCl early in development led to a persistent increase in MAP in adulthood.     

Angiotensin III-induced dipsogenic and pressor responses in rodents

Subcutaneous injections of [des-Asp1]-angiotensin I [( des-Asp1]-AI), angiotensin II (AII), and angiotensin III (AIII) induced drinking in the laboratory rat and the South American rodent Octodon degus, but not in the gerbil. In a second experiment, pretreatment with captopril, an angiotensin converting enzyme inhibitor, prevented the endogenous conversion of subcutaneously injected [des-Asp1]-AI to AIII and prevented drinking in rats and degus. The pharmacological artifact of hypovolemia caused by angiotensin-induced increases in vascular permeability was not observed in members of these species. In a final experiment blood pressure changes resulting from subcutaneous injections of AII and AIII in rats and gerbils were measured. Significant pressor elevations were seen following the administration of both analogues, although AII was more potent. These results demonstrate that AIII is dipsogenic in rats and degus and serves as a pressor agent in rats and gerbils. No ready explanation is available for the gerbil's relative lack of dipsogenicity to the presently tested angiotensins.     

Perinatal protein malnutrition enhances rewarding cocaine properties in adult rats

The rewarding properties of cocaine were assessed in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 40 days of age (deprived rats), as compared with well-nourished animals (control rats) using the conditioned place preference paradigm. Dose-response curves to cocaine (3, 5, 10, 15, 30, 45 or 60 mg/kg i.p.) revealed in deprived rats a conditioning effect with doses of 5 and 10mg/kg; doses of 15 and 30 mg/kg did not show any conditioning place preference and doses of 45 and 60 mg/kg revealed a significant aversive effect. In control rats, cocaine elicited place preference with doses of 10, 15 and 30 mg/kg, whereas 45 and 60 mg/kg did not show either conditioning or aversive effects. Furthermore, sensitization to the conditioning effect of cocaine was obtained in deprived animals with a low dosage of cocaine, that was ineffective in controls (5 mg/kg/day for 10 days). Related to the higher rewarding effects, sensitized deprived rats showed a selective and significant increase in FosB expression in nucleus accumbens (core and shell) and basolateral amygdala, brain areas related to the rewarding neuronal circuits. These results suggest that a deficient nutritional status during early life may induce in adult subjects an increased responsiveness to behavioral effects of cocaine and/or enhanced its reinforcement properties.     

Perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats

The present study was developed to ascertain whether or not susceptibility to lidocaine-kindling persists into adulthood in perinatal hypothyroid rats. Pregnant Wistar rats were randomly divided into two groups: the first one, a control group, that drank tap water; and a second one, a hypothyroid group, were treated with 0.02% propylthiouracil in their drinking water from the 14th gestational day to the 10th postpartum day. The pups of both groups were maintained with food and tap water ad libitum until the experiment was over. The pups of each group were divided to test the susceptibility to lidocaine-kindling at 30 and 100 days old, for this, lidocaine (50 mg/kg, i.p.) was administered daily. The seizures were usually present in the form of tonic attacks of fore and hind limbs, followed by intermittent clonic movements. An animal was considered kindled when it showed clonic movements for two consecutive days. We observed that the number of stimuli necessary to produce lidocaine-kindling seizures in hypothyroid rats was significantly lower than in the control group for both ages. Also, the percentage of kindled rats aged 30 days (73% and 89%) was greater than aged of 100 days (26% and 59%) in both control and hypothyroid groups, respectively. In conclusion, the perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats.     

Perinatal undernutrition reduced ethanol intake preference in adult recovered rats

Adult female rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) were tested for alcohol intake in a preference test. When compared with control animals, experimental rats exhibited higher overall fluid intake. Nevertheless, in terms of ethanol preference these subjects evidenced lower preference to this drug. A test for assessing ethanol olfactory preference did not show any differences between control and experimental rats in basal conditions. However, after repeated exposure to alcohol, deprived rats showed an aversion to ethanol odor, while controls evidenced the opposite effect, i.e., heightened preference. Possible differences to the aversive effects of ethanol between control and experimental animals were assayed by means of two taste aversion tests, by associating alcohol to sucrose or NaCl. No differences were detected between both groups of rats. These results demonstrate that early undernutrition reduces ethanol preference in a free choice situation. Such an effect could be due, at least partially, to odor aversion developed by repeated exposure.     

Effects of dietary NaCl deprivation during early development on behavioral and neurophysiological taste responses

In order to determine whether the gustatory system can be modified by restricting dietary NaCl during early development, neurophysiological taste responses were recorded in rats at various times after deprivation, and behavioral taste preferences were measured in adults. Rats deprived of dietary NaCl from the third day of gestation to 12 days postnatally and then placed on a NaCl-replete diet had chorda tympani nerve responses similar to those of nondeprived rats when recordings were made at 28 days of age and older; however, preferences for NaCl solutions over water were significantly less than those of controls when tested at adulthood. NaCl deprivation in pups from the third day of gestation to approximately 35 days postnatally resulted in altered chorda tympani nerve responses to NaCl but not to other stimuli such as NH4Cl and KCl. Therefore, restriction of dietary NaCl at a period in the rat's development when peripheral and central taste responses are changing results in short-term alterations in peripheral neural responses and in long-term changes in preference behaviors.     

Adrenoreceptor blockade in angiotensin-induced hypertension: effect on rat coronary arteries and myocardium

Adrenoreceptor blockade has been used to separate the actions of elevated blood pressure, angiotensin II, and catecholamines on the coronary vasculature and myocardium of rats. Twenty-two male Wistar-Kyoto rats received phentolamine (an alpha-receptor blocker, 10 mg/kg body weight) and/or propranolol (a beta-receptor blocker, 1 mg/kg body weight) followed by an infusion for 2 hours of angiotensin amide (1.7 micrograms/min/kg) or saline. Sections of left ventricle were examined by light and electron microscopy. Blood pressure was elevated only in animals receiving angiotensin II with or without propranolol. Epicardial arteries were devoid of lesions in all animals. Small intramural arteries and arterioles in the hypertensive animals exhibited vasoconstriction, endothelial cell vacuolization with bleb formation, and medial smooth muscle cell fragmentation and necrosis. Foci of irreversible ischemic or anoxic myocardial injury consisting of contraction zones and bands and translocated mitochondria with granular matrix densities were seen in angiotensin-infused animals. Similar but less severe myocardial changes were found in the animals pretreated with propranolol. Vascular lesions were also seen in animals receiving phentolamine, propranolol, and angiotensin II; but myocardial alterations consisted solely of areas with contraction zones. Vascular but not myocardial lesions were observed in animals that received angiotensin II and phentolamine. It is concluded that angiotensin II can produce vascular injury in the absence of elevated systemic blood pressure or catecholamine effects. In contrast, irreversible myocardial injury seems to depend upon the increased pressure and/or coronary artery vasoconstriction associated with angiotensin administration.     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Perinatal allopregnanolone influences prefrontal cortex structure, connectivity and behavior in adult rats

Cortical neurosteroid levels vary dramatically across development; during the second week of life elevated levels of allopregnanolone are associated with decreased GABA(A) receptor function. Since GABA(A) receptor modulation plays a role in proliferative regulation in developing neocortex, it is possible that endogenous neurosteroids such as allopregnanolone, acting through GABA(A) receptors, modulate cortical development. We augmented normally low levels with exogenous administration of allopregnanolone (10 mg/kg) during the first week of rodent life. The localization of parvalbumin-labeled cells was markedly altered; the ratio of cell number in the deep (layers V-VI) vs. superficial (layers I-III) layers of adult prefrontal cortex increased two-fold in rats administered allopregnanolone on postnatal day 1 or 5. The mechanism underlying these anatomical changes likely involves GABA(A) receptors because similar changes in interneuron placement were observed after neonatal benzodiazepine administration. Measures of mature cortical function were also altered after neonatal neurosteroid administration, including [(3)H]MK-801 binding, prepulse inhibition and amphetamine-induced locomotor activity. Moreover, neonatal allopregnanolone administration increases the number of parvalbumin-expressing neurons in medial dorsal nucleus of the thalamus while the total neuron number is decreased. These findings suggest that connectivity between the medial dorsal nucleus of the thalamus and prefrontal cortex is likely altered by neonatal neurosteroid administration and may result in a disinhibited frontal cortex. Disinhibition in the prefrontal cortex is associated with behavioral changes relevant to human psychosis and developmental disorders. If neurosteroids play a role in normal development of prefrontal/medial dorsal patency as suggested by these studies, then alterations in neurosteroid levels may contribute to abnormal neurodevelopment.     

Prenatal stress alters cardiovascular responses in adult rats

Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress.     

Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats

The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys. The abundance of renin mRNA in adrenal tissue was low and was estimated to be around 1% of that found in the kidneys. Adrenal renin mRNA levels also increased in animals kept on a low-salt diet and decreased in animals on high-salt diet. Taken together, our findings suggest that renin secretion and renin gene expression are inversely related to salt intake and that the influence of salt diet on these parameters has both transient and constant temporal components. Changes of blood pressure or nerve activity are not likely mediators of the effect of salt intake on renin expression. Since renal and adrenal renin mRNA levels change in parallel in response to alterations of salt intake we hypothesize the existence of a humoral factor that links renin expression to the rate of salt intake.     

Perinatal estradiol benzoate administration affects control of ventilation in adult male rats.

One injection of estradiol benzoate (EB) (100 micrograms) or vehicle was administered to male rat pups 5 days after birth. Two months later ventilation, ventilatory responses to 7% carbon dioxide, and to 580 mg/kg aspartic acid (an agent used as a marker of sexually dimorphism in the control of ventilation) were evaluated and body weight, testes weight, and nose-anus length were measured in animals in each group. The EB-treated rats had similar tidal volumes, frequency of breathing, and minute ventilation as did control male rats. The ventilatory responses of EB-treated rats to hypercapnia were markedly less than those of control animals. Aspartic acid administration depressed ventilation in control animals, but had no effect on ventilation in EB-treated males. Body and testes weights, as well as nose-anus length, were less in EB-treated compared with control rats. However, when body weight was normalized by nose-anus length and testes weight was normalized by body weight, the values were comparable between the two groups. Thus, perinatal EB treatment of male rat pups results in small, hypogonadal adult animals whose ventilation in response to hypercapnia was diminished and whose response to aspartic acid was female-like relative to those of control rats.     

Perinatal undernutrition facilitates morphine sensitization and cross-sensitization to cocaine in adult rats: a behavioral and neurochemical study

The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens “core” of D-rats. Similar DA levels were found in the nucleus accumbens “shell” and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats.     

Life-long dietary restriction affects striatally-mediated behavioral responses in aged rats

The effects of life-long dietary restriction on rotational behavior and stereotypy induced by intrastriatally administered dopamine-excitatory (dopamine, DA; amphetamine, AMPH) or cholinergic inhibitory (atropine, AT) agents were examined in rats. Three groups of male Wistar rats were used; mature ad lib (YAL, 6 month), old ad lib (OAL 24 month), and old restricted animals (OR). OR animals were fed and fasted on alternate days from weaning. Each rat was unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine and a cannula was implanted in the right caudate nucleus. Several doses of each drug [AT (0, 1, 7, micrograms) DA (0, 5, 50 micrograms), and AMPH (0, 2, 5, 5, 10 micrograms)] were given randomly (1 dose/day with 1 week between drugs). All doses of a particular drug were given before the next drug regimen was started. A combination of AMPH (25 micrograms) and AT (1 microgram) was also administered in one injection at the completion of all other regimens. Results showed that OR animals responded as well as YAL animals and far better than OAL animals following AMPH, DA, or low doses of AT. However, both the high dose of AT and the combined dose of AMPH-AT seemed to suppress responding in OR animals. Neither AT alone or AMPH-AT combinations had effects in OAL animals. Results are discussed in terms of the possible specificity of effects of dietary restriction on striatal functioning and behavior in senescence.     

Long-term dietary restriction influences plasma ghrelin and GOAT mRNA level in rats

The objective of this study was to examine the effect of chronic dietary restriction on the physical characteristics of the intestine and gut-derived satiety hormone production. Male Wistar rats (8 weeks) were randomized to ad libitum (AL) or 35% dietary restriction (DR) for 5 months. At the end of the study, physical measurements were made on the intestine and satiety hormone secretion and mRNA expression determined. A comparison group of young, growing AL rats (5 weeks) was also examined. The adult DR rats gained less weight over 5 months and had lower fat mass than adult AL rats (p < 0.05). The weight of the small intestine as a percentage of total body weight was greater in adult DR compared to adult AL but lower than young AL rats. Compared to AL, DR down-regulated proglucagon and cholecystokinin mRNA in the duodenum and ghrelin mRNA in the stomach of adult rats but was not different from young AL. Ghrelin-O-acyltransferase (GOAT) mRNA in the stomach was up-regulated 21-fold in adult AL rats compared to young AL and 14-fold compared to adult DR rats. Total and des-acyl ghrelin was approximately 50% higher in adult DR and young AL rats compared to adult AL. Plasma leptin and insulin were lower in adult DR and young AL rats compared to adult AL. Our findings suggest that long-term energy deficits continue to drive up ghrelin levels which may have profound implications for practical implementation of DR as an anti-aging or anti-obesity strategy in humans.     

Choline dietary supplementation improves LiCl-induced context aversion retention in adult rats

Previous studies have demonstrated that choline is an essential nutrient during prenatal and early postnatal developmental periods. Thus, the availability of choline during these periods produces some beneficial effects on hippocampal-dependent learning and memory in rats. However, research on the effect of adult choline supplementation on learning and memory abilities is scarce. In the present study, 3-4 month-old male Wistar rats receiving a 7-week choline-supplemented diet (4.5 fold that of a standard diet) and control rats receiving a standard diet were trained in a LiCl-induced contextual aversion task. Short and long-term context aversion retention was assessed by recording the consumption of a flavoured solution in the aversive and safe contexts over two subsequent tests. Statistical analysis showed that the supplemented group exhibited greater intake suppression in the aversive context than in the safe context when two retention tests were applied 3 and 15 days after conditioning. These results suggest that increasing dietary choline availability during adulthood may favour the retention of a context aversion.     

Perinatal methylmercury intoxication: Behavioral effects in rats

Sprague-Dawley rats were subjected to perinatal (4th gestational day until Postnatal Day 21) methylmercury intoxication to determine the long-term behavioral effect of the mercury poisoning. Experimental and control animals were evaluated at 110–140 days of age. Compared to controls, the methylmercury animals demonstrated significant behavioral deficits characterized by hypoactivity and by reduced appetitive, escape, and avoidance learning.