Effects of acute and chronic administration of exorphin C on behavior and learning in white rat pups

We studied the behavior of 21- and 35-day-old white rat pups in the “open field” and the learning of 36- to 41-day-old pups in a maze with food reinforcement. An opioid fragment of wheat gluten exorphin C (YPISL) was injected to pups chronically from day 1 to day 14 of their life or immediately prior to testing. We found that an acute peptide injection did not change animal behavior. The chronic intraperitoneal administration of the peptide at the same dose of 5 mg/kg significantly increased exploratory activity, decreased anxiety, and improved learning. Delayed exorphin C effects were more expressed in female rats.     

Peculiarities of exploration behavior of socially deprived rats in stress situation

Male Wistar rats (n = 18) were studied at the age of 120 days after social deprivation in the period from the 22nd to 70th days of postnatal development. They displayed significant lower activity in the open field, elevated plus-maze, and Porsolt test than control animals (n = 19). Decreased exploratory activity was found to be related with higher level of anxiety. This was confirmed by their avoidance of open arms of the elevated plusmaze and reactions to approaching hand. These animals had problems in the maze arm choice. They showed low time variability of choice-related actions (waiting in the center of the open field or elevated plus-maze and change in the movement direction along an open-field wall, including the movement per se, and arm choice and changing, i.e., alternative choice). Shorter time of choice-related actions was observed in situations of unequal alternatives.     

Effects of 5-HT1A receptor agonist and antagonist on anxiety in intact and ovariectomized female rats

The purpose of this work was to study the role of 5-HT1A receptors on the level of anxiety in adult intact and ovariectomized (OVX) female rats. The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) given for 14 days alone or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on behavior in the elevated plus maze. In intact females administration of NAN-190 resulted in significant increase in the number of enterings and the time spent on the open arms in every phase of the estrous cycle, however, 8-OH-DPAT failed to modify these parameters. In OVX females 8-OH-DPAT alone or in combination with 17beta-estradiol significantly increased the number of enterings and time spent on the open arms. On the contrary, NAN-190 alone or in combination with 17beta-estradiol in OVX females failed to evoke behavioral changes in the elevated plus maze. Thus, the 5-HT1A receptor antagonist NAN-190 induced anxiolytic effect in intact female rats, while 5-HT1A receptor agonist 8-OH-DPAT produced an anxiolytic profile on OVX rats. Results of this work specify the involvement of 5-HT1A receptors in behavioral mechanisms of anxiety in OVX female rats.     

Effect of harmaline on firing pattern of rat cerebellar Purkinje cells in ontogenesis

In this work, responses of rat Purkinje cells to intraperitoneal administration of the hallucinogenic alkaloid harmaline (0.15 mg/kg) were studied in the course of ontogenesis. The experiments were carried out on Wistar rats of three age groups: rat pups (13-18 days), adult animals (2-7 months), and aged rats (25-36 months). In Purkinje cell firings, two types of electric reactions were revealed; they were similar in all age group of the animals. In cells with the 1st type of reactions, in response to the harmaline administration there was recorded a significant increase of frequency of complex spikes, accompanied by disappearance of simple spikes. In the activity of Purkinje cells of the 2nd type, the complex spike frequency also increased; however, the firing simple spikes were preserved, although with a decrease of their frequency as compared with norm. Essential changes of activity of the cerebellar Purkinje cells were found in the rat pups and aged animals in comparison with adult rats, which agrees well with immaturity of various cerebellar structures in the first case and with involutionary changes in the second case.     

Effect of insulin and 2-deoxy-d-glucose on the food intake of infant rats

The effects of glucoprivation on the food intake have been determined in infant rats up to weaning. It was found that insulin reduced the milk intake of 9, 13 and 17-day-old males and females for three hours after treatment. In 24-day-old pups food intake increased for three hours after insulin administration, and decreased during the next 21-hour period. 2-deoxy-D-glucose increased the food intake in 28-day-old rat pups only. It was concluded that the inability of rat pups to correct glucoprivation by a subsequent increase of food intake is a consequence of the inadequate development of hypothalamic regulatory mechanisms. Glucoprivation stimuli are ineffective inducers of short-term hyperphagia of rat pups until the age of 24-28 days.     

Effect of Time of Separation from Mother on Behavior in Open Field and on State of the Sympathoadrenal System in Rats Reared under Conditions of Social Isolation

The level of catecholamine excretion with urine and behavior in the open field test were studied in male Wistar rat pups separated from female at the age of 17, 21, 30, and 36 days and reared subsequently for 40 days under conditions either of social isolation or in the group with their kin. It was shown that in rats weaned at the age of 17 and 21 days, the subsequent rearing in isolation led to an increase of the urinary excretion of adrenaline and a decrease, of noradrenaline. After isolation at the 30th day, there was revealed an increase of the excretion level both of adrenaline and of noradrenaline. The social isolation also leads to an increase of horizontal motor activity in rats weaned at the age of 17 days and to a decrease of this activity in rats weaned at the 30-day age. After isolation at the age of 21 days, an earlier extinguishing of the activity it was observed at repeated testing. Isolation at the age of 36 days, on the contrary, led to a decrease of the extinguishing process. Thus, it is shown that the social isolation produces changes in rat behavior and has a stress effect on the animals; the effect of isolation depends on duration of the rearing of rats in the nest with the female.     

The effect of age and 1,25-dihydroxyvitamin D3 treatment on the intestinal calcium-binding protein of suckling rats.

The intestinal level of the vitamin D-dependent duodenal calcium-binding protein was assayed by an equilibrated column technique in rat embryos, neonates, and pups. Calcium-binding protein was undetectable in unborn, newborn, and 1- to 2-day-old rats i.e., the level was lower than in severely vitamin D-deficient animals. Calcium-binding protein was detected after the animals were 5-days old and thereafter rose monotonically as a function of body weight. Treatment with 1,25-dihydroxyvitamin D₃ failed to raise the calcium-binding protein levels of newborn or 1-day-old rats, but doubled the level in 11- or 12-day-old pups. Plasma calcium was raised in all treated animals. The failure to detect calcium-binding protein in vitamin D-replete suckling animals provides evidence for a dissociation between calcium absorption and calcium binding protein.     

Dizocilpine pretreatment suppresses the action of hypoxia on hippocampal epileptic afterdischarges in immature rats

Effect of dizocilpine (0.5 mg/kg i.p.) on epileptic afterdischarges elicited by low-frequency electrical stimulation of the dorsal hippocampus was studied in rat pups aged 12 and 18 days. Repeated elicitation of afterdischarges (ADs) in control animals resulted in a progressive increase of the duration of ADs in both age groups. Dizocilpine (MK-801) injected after the first afterdischarge suppressed this prolongation in 12-day-old rats only. Hypobaric hypoxia (simulated altitude of 9000 m for one hour) led to a marked prolongation of the first afterdischarge in both age groups with a tendency to shorter ADs after repeated stimulations. Dizocilpine potentiated this tendency in 12-day-old rat pups so that it became statistically significant. Administration of dizocilpine before hypoxia prevented the increase in duration of the first afterdischarge in both age groups.     

Effect of harmaline on firing pattern of rat cerebellar Purkinje cells in ontogenesis

In this work, responses of rat Purkinje cells to intraperitoneal administration of the hallucinogenic alkaloid harmaline (0.15 mg/kg) were studied in the course of ontogenesis. The experiments were carried out on Wistar rats of three age groups: rat pups (13–18 days), adult animals (2–7 months), and aged rats (25–36 months). In Purkinje cell firings, two types of electric reactions were revealed; they were similar in all age group of the animals. In cells with the 1st type of reactions, in response to the harmaline administration there was recorded a significant increase of frequency of complex spikes, accompanied by disappearance of simple spikes. In the activity of Purkinje cells of the 2nd type, the complex spike frequency also increased; however, the firing simple spikes were preserved, although with a decrease of their frequency as compared with norm. Essential changes of activity of the cerebellar Purkinje cells were found in the rat pups and aged animals in comparison with adult rats, which agrees well with immaturity of various cerebellar structures in the first case and with involutionary changes in the second case.     

Static magnetic field exposure affects behavior and learning in rats

The present work investigated the behavioral effects of a moderate exposure (1 h per day for 5 consecutive days) to a static magnetic field (SMF, 128 mT) in male rats. SMF effects were evaluated in two sets of control and SMF-exposed rats. One set of animals was used for evaluation of SMF potential effects on emotional behaviors in the elevated plus maze and in the open field. The other set of animals was tested for learning and memory abilities in different procedures of the Morris water maze task. We found no significant difference between control and SMF-exposed rats in anxiety tests. However, the ratio of open arms time in the plus maze was reduced by half in SMF-exposed rats. In the Morris water maze, SMF-exposed rats were partially impaired during the initial learning task as well as in the retention task at one week. We conclude that static magnetic field exposure altered emotional behaviors in the plus maze and led to cognitive impairments, or at least to substantial attention disorders, in the Morris water maze.     

Effect of harmaline on the complex spike shape and depression time in cerebellar Purkinje cell discharge in rat postnatal ontogenesis

Functional relationship between wave form of complex spike (CS) and depression time of simple spike (SS) in discharge of cerebellar Purkinje cells was studied after their activation with afferent climbing fiber at different terms of postnatal ontogenesis in norm and after treatment with harmaline. The experiments were carried out on three age groups of Wistar rats: rat pups (2 weeks), the adult (4–6 months), and the old animals (22–26 months). It was established that the SS duration in norm was approximately equal in rat pups, adult, and old animals, whereas it markedly decreased form the young to the old animals during the SS depression in the Purkinje cell discharge. Frequency of small action potential (lAP) and their number in the Purkinje cell discharge were approximately equal in young rat pups and adult animals, while in old animals these parameters were higher, on average, by 30%. After administration of harmaline, all CS parameters in rat pups and old animals increased in parallel with the depression time elongation. In adult rats, harmaline did not produce statistically significant changes of the mean values of CS parameters, but an increase of the simple spike depression time was observed. The obtained results allow concluding that the SS wave form and the simple spike depression time in norm are functionally coupled and change with age. The effect of harmaline on the CS wave forms as well as on interrelation of the CS duration and the CS depression time in the Purkinje cell discharge was more pronounced at the early and the late stages of Wistar rat postnatal ontogenesis.     

Effects of dieldrin on hepatic carbohydrate metabolism in the suckling and adult rat

Hepatic carbohydrate metabolism was studied in adult and suckling rats given age-specific LD50 doses of dieldrin po. These doses in 5-, 10-, and 60-day-old Wistar rats were 38, 28, and 63 mg/kg, respectively. Plasma glucose and free fatty acids (FFA), and hepatic glycogen, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), and glucose-6-phosphatase (G6P) were measured 1 and 3 h after administration of the insecticide. Plasma glucose concentrations were elevated (17%) in some 5-day-old rats after 1 h and in all adults after 1 and 3 h (45 and 30%, respectively). Plasma FFA concentrations were decreased (9%) in the 5-day-old rat 1 h after dieldrin. Hepatic glycogen content was reduced in both 5- and 10-day-old pups at 1 hour (22 and 17%, respectively). Hepatic FDP activity was elevated in the 5-day-old rat at 1 h (17%) and was decreased (10%) in the 10-day-old rat at 3 h. Hepatic PEPCK activity was increased in adult animals by 30% 1 h after dieldrin. Furthermore, PEPCK activity was increased at 3 h in rats of all ages (76%, 5-day-old pup; 115%, 10-day-old pup; 56%, 60-day-old adult). Hepatic G6P activity was unaltered by dieldrin. Thus only the activity of hepatic PEPCK is consistently elevated by dieldrin exposure. However, this enhanced PEPCK activity is associated with dieldrin-induced hyperglycemia only in the adult rat.     

Long term neurological and behavioral effects of graded perinatal asphyxia in the rat

Perinatal hypoxic-ischemic states can cause irreversible damage to the brain, ranging from minimal brain dysfunction to death. Only few studies have been reported describing neurological, cognitive and behavioral deficits following perinatal asphyxia. We therefore decided to study long term effects of perinatal asphyxia in a well-documented animal model resembling the clinical situation. Caeserean section in rats was performed and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 5-20 min; pups were then given to surrogate mothers and examined at three month of age. Examinations consisted of a battery of motor and reflex tests, Morris water maze, multiple T-maze, elevated plus maze and open field studies. No abnormalities were found in rats even with long periods of perinatal asphyxia by neurological examination, in the open field and in mazes. Interestingly, in the elevated plus maze rats with long lasting exposure to hypoxia (15 and 20 min of asphyxia) showed reduced anxiety-related behavior. This finding may be relevant for the explanation of anxiety related disorders in adulthood with a tentative history in the perinatal period.     

Age-related changes in activity of cerebellum Purkinje cells,shape of the complex spike,and locomotion of Wistar rats under effect of ethanol

The work deals with study of peculiarities of effect of ethanol upon the Purkinje cell activity, shape of the complex spike, and locomotion of rats at different stages of ontogenesis, such as the stage of the morphofunctional maturation of the cerebellar cortex, the mature stage, and in the process of aging. The experiments were carried out on three age groups of Wistar rats: rat pups (2 weeks), adult rats (3–6 months), and senile animals (22–26 months). The administration of ethanol has been established to produce an increase in frequency of simple spikes, a decrease in frequency of complex spikes, a shortening of duration of depression of simple spikes, a decrease in the total duration of the complex spike, the number and frequency of its impulses as well as reduction of the motor activity of animals of all age groups. The change of the majority of the studied parameters occurred by the common temporal scheme. The earliest responding were the rat pups, later-the adult rats, and the last-the animals of the senior group. The stronger effect of ethanol was observed in adult rats. Their differences of all studied parameters, as compared with rat pups and senile animals, were characterized on the whole by the longer period of time and by the higher percent of changes relative to the initial values. Analysis of the obtained results has shown that the most pronounced changes in parameters of the cerebellum Purkinje cell activity and of the complex spike shape corresponded to the more significant decrease in the locomotion level, i.e., were recorded in adult rats. Thus, the work has demonstrated different sensitivity to administration of ethanol in the Wistar rats at different stages of ontogenetic development.     

Effect of phenobarbitone administration to pregnant rats on anxiety in offsprings

Adults Charles-Foster rats were prenatally treated to phenobarbitone (10 mg/kg, i.p.) from day 13 to 21 of gestation, this being the critical period of neural development. Pregnant control rats were similarly treated with equal volume of vehicle. Adult rat offsprings at 8-9 weeks of age were subjected to open-field exploratory behaviour, elevated plus-maze and elevated zero-maze tests. The rat offsprings displayed significantly increased ambulation and rearings in an open-field arena when compared to control offsprings whereas self-grooming and faecal droppings remain unchanged. On elevated plus-maze test these prenatally treated rat offsprings spent significantly less time on open arms and more time and more number of entries in enclosed arms as compared to controls. Prenatally exposed rats also showed significant less time on open arms, less number of head dips and stretched attend postures on elevated zero-maze test indicating increased anxiogenic behavioural pattern in these animals. The results suggest that prenatal exposure to phenobarbitone leaves a lasting effect on the anxiety state of the offsprings.     

Antipentylenetetrazol action of clobazam in developing rats

Clobazam (0.5 to 7.5 mg/kg i.p.) was tested against motor seizures elicited by pentylenetetrazol in rats 7, 12, 18, 25 and 90 days old. Minimal, predominantly clonic seizures with preserved righting ability were reliably induced by pentylenetetrazol and suppressed by clobazam in rats aged 18 days or more. The incidence of minimal seizures after clobazam pretreatment was not increased in 7- and 12-day-old rat pups. Generalized tonic-clonic seizures were markedly suppressed by clobazam in all age groups. In 18-day-old and older animals clobazam doses suppressing generalized seizures were always lower than those necessary for exerting an effect on minimal seizures. The differences in clobazam action appearing at various levels of maturation are only quantitative.     

Impact of chronic ethanol intake of rat mothers on the seizure susceptibility of their immature male offspring

The aim of present study was to examine the impact of prenatal ethanol exposure on seizure susceptibility of the offspring. Pregnant Wistar rats were compelled to drink either 10% or 20% ethanol solution, as the only drinking fluid since conception up to the weaning of their offspring at the age of 28 days. Pregnant and nursing rats of the control group drank water. Electrophysiological experiments (repeated electrical stimulation and analysis of cortical afterdischarges duration) were than performed on their immature offspring. Rat pups were tested on postnatal day 18, 25, and 35. Shortening of afterdischarges duration was observed in 18-day-old animals (mothers drank 20% ethanol) when compared with age matched controls and failure of post-ictal depression phenomenon was found in 25- and 35-day-old animals. Our findings signalize that ethanol exposure during pregnancy influences seizure susceptibility by acting on excitatory/inhibitory brain systems and this effect is dose- and age-dependent.     

Reduced anxiety in postpartum rats requires recent physical interactions with pups, but is independent of suckling and peripheral sources of hormones

Changes in emotional behavior occur across the reproductive cycle in female rodents, with reduced anxiety found during the postpartum period, but relatively little is known about factors contributing to this decreased anxiety. Using increased duration of time spent in the open arms of an elevated plus-maze as an indicator of reduced anxiety, it was found in a series of experiments that (1) anxiety is significantly reduced in Long-Evans females during the first week of lactation, but not thereafter, (2) relatively recent contact with pups before testing (within 4 h) is necessary for their reduced anxiety, (3) dams that receive only distal sensory cues from pups for the 4 h prior to testing do not show reduced anxiety, (4) the absence of nipples, and therefore a lack of suckling by pups, has no effect on dams' anxiety, (5) cesarean delivery of pups 2 days prior to expected parturition did not alter later anxiety in dams, (6) hypophysectomy during mid-pregnancy or ovariectomy within 24 h after parturition also did not prevent reduced anxiety in dams, and (7) differences in anxiety between lactating and virgin females are greatest 4-8 min after being placed in the plus-maze. Therefore, exposure to their own peripheral hormones through mid-pregnancy is sufficient to prime female rats to show reduced anxiety, but only if they later have recent physical interaction with pups. Furthermore, because suckling and the peripheral hormones released during suckling appear to be unnecessary, decreased anxiety in maternal rats may instead be regulated by the transient intracerebral release of neuropeptides or neurotransmitters while dams receive other types of tactile inputs from their infants.     

Obestatin improves memory performance and causes anxiolytic effects in rats

Obestatin is a peptide hormone that is derived from the same polypeptide precursor (preprogrelin) as ghrelin, but it acts in opposing way on ingestive behavior. Our previous studies showed that ghrelin affects memory and anxiety. Here, we studied the possible effects of icv obestatin injection in rats upon memory retention (using two different paradigms), anxiety like behavior (plus maze test), and food intake. Obestatin induces an increase in the percentage of open arms entries (Obestatin 3.0nmol/rat: 61.74+/-1.81), and percentage of time spent in open arms (Obestatin 3.0nmol/rat: 72.07+/-4.21) in relation to the control (33.31+/-1.54; 25.82+/-1.68), indicating an anxiolytic effect. The two doses of obestatin increased latency time in a step down test and the percentage time of novel object exploration, suggesting that the peptide influences learning and memory processes that involve the hippocampus and the amygdala. This report provides evidence indicating that obestatin effects are functionally opposite on anxiety and hunger to the ghrelin effects, while both these related peptides increase memory retention.     

The effect of the limitation of afferent inflow in early ontogeny on the evoked activity of projective neurons depends on the degree of the maturity of the sensory inputs]

The study is focused on the influence of a partial limitation of the sensory inflow in rat pups on the development of the sensory systems, which mature earlier and later. In accordance with the ontogenetic rule of proximal-distal maturation, the sensory inflow from the forelimbs matures faster than that from the hindlimbs. Fourteen Wistar rat pups (from 28) were deafferented on the 13th day of postnatal ontogeny (a small portion of the median nerve was unilaterally dissected). The background and evoked activity of single neurons was recorded in 26-47-day-old pups in the somatosensory cortex (in the projection areas of the intact n. medianus, which matures earlier, and n. ischiadicus, which matures later). The changes in firing activity produced by deafferentation were observed. In the projection area of the intact forelimb of the denervated rats, the incidence of inhibitory responses significantly increased, whereas the incidence of completes responses significantly decreased. In the hindlimb projection area of the denervated animals the background firing rate was significantly lower and the incidence of activation responses was increased.