Regulation of TGF-beta ligand and receptor expression in neonatal rat lungs exposed to chronic hypoxia.

Long-term effects of hypoxia are largely due to its modulatory effects on proliferation and differentiation of epithelial and endothelial cells, processes also regulated by the transforming growth factor (TGF)-beta system. We investigated the effects of hypoxia on the TGF-beta system in rat lungs from different developmental stages. Sprague-Dawley rats were exposed to 9.5% oxygen during either the first 2 wk of life or adulthood. Analysis revealed an arrest of alveolarization in hypoxic postnatal day 14 rats. Bioactive TGF-beta levels in bronchoalveolar lavage fluid were increased in these animals, and Western blot analysis revealed upregulation of TGF-beta receptor (TbetaR) I and II. None of these changes was observed in hypoxic adults. Hypoxia did, however, lead to decreased expression of TbetaRIII in both postnatal day 14 and adult rats. Immunohistochemical analysis localized TbetaRI-III predominantly to bronchiolar and alveolar epithelium; these patterns did not change with hypoxia. Thus we observed changes in TGF-beta activity and TbetaR isotype expression in rat lung that parallel the arrest in alveolarization seen with chronic hypoxia in early development. These alterations may partly explain the morphological changes observed in hypoxia.     

Mitigation of behavioral deficits and cognitive impairment by antioxidant and neuromodulatory potential of Mukia madrespatana in D-galactose treated rats

Plants and their parts have been extensively used for the therapeutic purposes such as aging due to their powerful antioxidative belongings. Presently, we intended to examine the consequence of fruit peel of Mukia madrespatana (M.M) on D-galactose (D-Gal) persuaded anxiety and/or depression profile, cognition and serotonin metabolism in rats. Animals were divided in to 4 groups (n = 6). (i) Water treated (ii) D-Gal treated (iii) M.M. treated (iv) D-Gal + M.M. treated. All the animals received their respective treatment for 4 weeks. D-Gal and M.M. fruit peel were given to animals with oral gavage with doses 300 mg/ml/kg/day and 2 g/kg/day respectively. After 4 weeks’ behavioral analysis performed to evaluate anxiety and depression profile, cognitive function of animals. After that animals were sacrificed and whole brain removed for biochemical (redox status, degradative enzyme of acetylcholine), and neurochemical (serotonin metabolism) analysis. Results showed that administration of M.M. inhibited D-Gal-instigated anxious and depressive behaviors and improved cognition. Treatment of M.M. decreased MDA levels, AChE activity and increased antioxidant enzyme activity in D-Gal administered and control rats. Enhanced serotonin metabolism also decreased by M.M. in control and D-Gal administered rats. In conclusion, M.M. fruit peel has powerful antioxidative and neuromodulatory properties and due to this effect, it may be a good source of mitigation/treatment for aging induced behavioral and cognitive impairment.     

Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT_1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala.     

Folic Acid Prevents Behavioral Impairment and Na+,K+-ATPase Inhibition Caused by Neonatal Hypoxia–Ischemia

Folic acid plays an important role in neuroplasticity and acts as a neuroprotective agent, as observed in experimental brain ischemia studies. The aim of this study was to investigate the effects of folic acid on locomotor activity, aversive memory and Na(+),K(+)-ATPase activity in the frontal cortex and striatum in animals subjected to neonatal hypoxia-ischemia (HI). Wistar rats of both sexes at postnatal day 7 underwent HI procedure and were treated with intraperitoneal injections of folic acid (0.011 μmol/g body weight) once a day, until the 30th postnatal day. Starting on the day after, behavioral assessment was run in the open field and in the inhibitory avoidance task. Animals were sacrificed by decapitation 24 h after testing and striatum and frontal cortex were dissected out for Na(+),K(+)-ATPase activity analysis. Results show anxiogenic effect in the open field and an impairment of aversive memory in the inhibitory avoidance test in HI rats; folic acid treatment prevented both behavioral effects. A decreased Na(+),K(+)-ATPase activity in striatum, both ipsilateral and contralateral to ischemia, was identified after HI; a total recovery was observed in animals treated with folic acid. A partial recovery of Na(+),K(+)-ATPase activity was yet seen in frontal cortex of HI animals receiving folic acid supplementation. Presented results support that folic acid treatment prevents memory deficit and anxiety-like behavior, as well as prevents Na(+),K(+)-ATPase inhibition in the striatum and frontal cortex caused by neonatal hypoxia-ischemia.     

Dynamics of hypothalamic CRH immune reactivity in active and passive rats in the course of development of behavioural depression

A possible relation between activity of the main CRH-producing centers of hypothalamus and depressive-like behavior of animals was studied. We used genetically selected strains--KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats, demonstrating active and passive strategy of adaptive behavior in novelty situaltions, respectively. Rats were exposed to inescapable stress to develop a "learned helplessness". We observed considerable differences between two strains of animals in CRH-expression in parvo-, magno-cellular parts of the paraventricular nucleus and in the supraoptic nucleus in the course of behavioral depression development. Significant differences between control groups were seen only in paraventricular nucleus. On the 1st post-stress day in hypothalamus of KLA rats, we detected decreased CRH immune reactivity that remained unchanged up to the 10th day. In KHA rats, there were no notable changes of CRH expression in all studied nuclei. These findings, including previous results on different dynamics of behavioral changes and different hypothalamo-pituitary-adrenocortical system activity during development of depression in KLA and KHA rats, indicate that "learned helplessness" in these two groups of animals provides the model analogues of different types of depression. Besides, these findings indicate different implication of hypothalamus CRH-system in the behavioral depression development in rats with divergent strategy of adaptive behavior.     

Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus

Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of β1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1_A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.     

Effects of Voluntary Alcohol Intake on Risk Preference and Behavioral Flexibility during Rat Adolescence

Alcohol use is common in adolescence, with a large portion of intake occurring during episodes of binging. This pattern of alcohol consumption coincides with a critical period for neurocognitive development and may impact decision-making and reward processing. Prior studies have demonstrated alterations in adult decision-making following adolescent usage, but it remains to be seen if these alterations exist in adolescence, or are latent until adulthood. Here, using a translational model of voluntary binge alcohol consumption in adolescents, we assess the impact of alcohol intake on risk preference and behavioral flexibility during adolescence. During adolescence (postnatal day 30–50), rats were given 1-hour access to either a 10% alcohol gelatin mixture (EtOH) or a calorie equivalent gelatin (Control) at the onset of the dark cycle. EtOH consuming rats were classified as either High or Low consumers based on intake levels. Adolescent rats underwent behavioral testing once a day, with one group performing a risk preference task, and a second group performing a reversal-learning task during the 20-day period of gelatin access. EtOH-High rats showed increases in risk preference compared to Control rats, but not EtOH-Low animals. However, adolescent rats did a poor job of matching their behavior to optimize outcomes, suggesting that adolescents may adopt a response bias. In addition, adolescent ethanol exposure did not affect the animals'' ability to flexibly adapt behavior to changing reward contingencies during reversal learning. These data support the view that adolescent alcohol consumption can have short-term detrimental effects on risk-taking when examined during adolescence, which does not seem to be attributable to an inability to flexibly encode reward contingencies on behavioral responses.     

Postnatal handling reverses social anxiety in serotonin receptor 1A knockout mice

Mice lacking the serotonin receptor 1A (Htr1a knockout, Htr1a ^KO ) show increased innate and conditioned anxiety. This phenotype depends on functional receptor activity during the third through fifth weeks of life and thus appears to be the result of long-term changes in brain function as a consequence of an early deficit in serotonin signaling. To evaluate whether this phenotype can be influenced by early environmental factors, we subjected Htr1a knockout mice to postnatal handling, a procedure known to reduce anxiety-like behavior and stress responses in adulthood. Offspring of heterozygous Htr1a knockout mice were separated from their mother and exposed 15 min each day from postnatal day 1 (PD1) to PD14 to clean bedding. Control animals were left undisturbed. Maternal behavior was observed during the first 13 days of life. Adult male offspring were tested in the open field, social approach and resident–intruder tests and assessed for corticosterone response to restraint stress. Knockout mice showed increased anxiety in the open field and in the social approach test as well as an enhanced corticosterone response to stress. However, while no effect of postnatal handling was seen in wild-type mice, handling reduced anxiety-like behavior in the social interaction test and the corticosterone response to stress in knockout mice. These findings extend the anxiety phenotype of Htr1a ^KO mice to include social anxiety and demonstrate that this phenotype can be moderated by early environmental factors.     

Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-alpha

Early life events and childhood infections have been associated with the development and onset of inflammatory bowel disease in adulthood. However, the consequences of neonatal infection in the development and severity of colitis are not established. We investigated the effects of a neonatal (postnatal day 14) or juvenile (postnatal day 28) immune challenge with LPS on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats developed more severe colitis than control animals, reflected in a greater loss of weight and a significantly increased macroscopic tissue damage score. These findings were associated with a hypothermic response after TNBS treatment in nLPS rats, but not in neonatally saline-treated rats receiving TNBS. These differences were not seen after TNBS in rats that had received LPS on postnatal day 28. Plasma corticosterone was measured as an index of adult hypothalamic-pituitary-adrenal (HPA) axis activation as was TNF-alpha, a proinflammatory cytokine associated with inflammatory bowel disease. Four days after TNBS treatment, plasma corticosterone was unaltered in all groups; however, TNF-alpha was significantly increased in adult TNBS-treated rats that had LPS as neonates compared with all other groups. In conclusion, neonatal, but not later, exposure to LPS produces long-term exacerbations in the development of colitis in adults. This change is independent of HPA axis activation 4 days after TNBS treatment but is associated with increased circulating TNF-alpha, suggestive of an exaggerated immune response in adults exposed to neonatal infection.     

Effect of serotonin on the formation of neurons producing gonadotropin-releasing hormone in Wistar rats

The effect of serotonin on the formation of neurons producing gonadotropin-releasing hormone (GnRH) during embryogenesis of Wistar rats was studied. The neurons producing GnRH were detected immunocytochemically on days 18 and 21 of embryonic development and on day 15 of postnatal development of rats with normal serotonin metabolism and rats in which the synthesis of serotonin was inhibited by p-chlorophenylalanine. The total number of GnRH neurons in serotonin deficiency was larger than in the case of its normal metabolism at all developmental stages studied. This is an indirect evidence for the inhibitory effect of serotonin on the formation of GnRH neurons. To confirm the morphogenetic effect of serotonin, we studied the rate of formation of GnRH neurons by injecting bromodeoxyuridine in the formation period of these neurons. It was found that serotonin deficiency had no effect on the time of formation of GnRH neurons: over 97% of neurons formed on days 11 to 15 of embryonic development both in the experimental and control groups. Note that, in serotonin deficiency, the maximum number of GnRH neurons formed one day later than in the normal state. Thus, serotonin inhibits the proliferation of GnRH neuron progenitor cells and thereby has a morphogenetic effect on the development of these neurons.     

Effect of deafferentation of the forelimb on the postnatal development of the synaptic plasticity in the hippocampus

The postnatal development of LTP in CA1 area of hippocampus was studied in hippocampal slices from 13-20-day-old intact rats, after unilateral resection of n. medianus on the 13th day, and sham-operated animals. In slices from the intact rats prepared on the 15th-16th-day of postnatal development, the LTP magnitude and duration were significantly larger than in adult animals. Partial deafferentation eliminated this overshoot. However, a less pronounced increase in synaptic plasticity was observed in operated animals on the 17th day. The LTP suppression in the experimental animals may be explained by a decrease in the NMDA receptor activity due to enhanced synaptic activity in the hippocampus. We think that the limited sensory inflow from the partially deafferented forelimb to the hippocampus via the entorhinal cortex may be compensated by activation of other inputs from specific or/and nonspecific pathways. In contrast, the LTP magnitude and duration were significantly increased in slices from the sham-operated rats. This increase may be explained by a decline of synaptic activation of the hippocampus under anesthesia.     

Correlation of membrane-bound and free ribosomes in normal rat liver, Zajdela hepatoma rat liver and ascite cells proper]

The content of membrane-bound ribosomes in normal rat liver cells is 3 times as high as compared to that of free ribosomes. (K=membrane-bound ribosome RNAs divided by free ribosome RNAs=3, the opposite effect being observed in case of ascites hepatoma cells. A considerable increase in the free ribosome fraction in the liver of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of membrane-bound ribosomes (K=0.6). Similar, but less-pronounced changes were observed in liver cells of control animals after 48-hour starvation (K=0.9), simulating the condition occurring during the last days of tumour animals' life. Thus, changes in the rativ of membrane-bound to free ribosomes in liver during the ascites tumour growth are probably specifics and are not only due to anorexia in Zajdela hepatoma animals.     

Frontal deafferentation of the mediobasal hypothalamus in the neonatal rat and its effects on the preoptico-infundibular LHRH-tract

Summary By use of the peroxidase-antiperoxidase-complex (PAP) immunohistological method, the preoptico-infundibular LHRH-tract was studied in adult female rats in which frontal hypothalamic deafferentation was performed at the third or tenth postnatal day. In the former group, this LHRH-tract appeared to be similar to that of the intact controls; the animals showed regular vaginal cycles and ova were present in their oviducts. In the latter group, however, marked reduction in the number of the LHRH-nerve fibers was observed behind the sites of the deafferentation in the mediobasal hypothalamus (MBH), whereas LHRH-immunoreactive perikarya and nerve fibers containing the immunoreactive material were seen rostral to the plane of severance. In these animals reduction of LHRH-fibers in the MBH was accompanied by an anovulatory syndrome characterized by constant vaginal cornification and polyfollicular ovaries. Comparing the glial scar formation induced by the cut, significant differences were detected between the two experimental groups. In the animals deafferented on the 3rd day of life, reduction of nerve cells was seen along the cut, but LHRH-fibers crossing the thin glial scar were detectable in large numbers. On the other hand, in the animals deafferented on the 10th postnatal day, extensive glial scar tissue appeared to interrupt the LHRH-fibers rostral to the cut.     

Effects of long-term exposure to 900 megahertz electromagnetic field on heart morphology and biochemistry of male adolescent rats

The pathological effects of exposure to an electromagnetic field (EMF) during adolescence may be greater than those in adulthood. We investigated the effects of exposure to 900 MHz EMF during adolescence on male adult rats. Twenty-four 21-day-old male rats were divided into three equal groups: control (Cont-Gr), sham (Shm-Gr) and EMF-exposed (EMF-Gr). EMF-Gr rats were placed in an EMF exposure cage (Plexiglas cage) for 1 h/day between postnatal days 21 and 59 and exposed to 900 MHz EMF. Shm-Gr rats were placed inside the Plexiglas cage under the same conditions and for the same duration, but were not exposed to EMF. All animals were sacrificed on postnatal day 60 and the hearts were extracted for microscopic and biochemical analyses. Biochemical analysis showed increased levels of malondialdehyde and superoxide dismutase, and reduced glutathione and catalase levels in EMF-Gr compared to Cont-Gr animals. Hematoxylin and eosin stained sections from EMF-Gr animals exhibited structural changes and capillary congestion in the myocardium. The percentage of apoptotic myocardial cells in EMF-Gr was higher than in either Shm-Gr or Cont-Gr animals. Transmission electron microscopy of myocardial cells of EMF-Gr animals showed altered structure of Z bands, decreased myofilaments and pronounced vacuolization. We found that exposure of male rats to 900 MHz EMF for 1 h/day during adolescence caused oxidative stress, which caused structural alteration of male adolescent rat heart tissue.     

Glucose tolerance of postnatally stress-sensitized albino rats following chronic emotional stress in adulthood]

Male albino rats were used to study the effect of electrical stimulation in the postnatal phase (day 1--15) leading to short-time convulsions and cyanosis lasting about 10 min in 5-month-old animals upon the development of glycemic dysregulation induced by emotional stress. The studies involving i.p. glucose administration show that a 3-week stress influence on postnatally stimulated animals caused heavier changes of glycemic regulation than with non-pretreated animals. These results suggest a stress sensitization occurring in the postnatal phase and are discussed in connection with the "stress-sensitive risk personality" by R. BAUMANN. Further studies have shown that the postnatal stress sensitiveness is reversible and cannot only be compensated by a rest period of several weeks but may even cause stress resistance on renewed stressing for three weeks.     

The action of proinflammatory cytokines on formation of behavior during early postnatal ontogenesis

The study is devoted to the role of proinflammatory cytokine-interleukin-1beta during early postnatal ontogenesis in formation of behavioral programs. Cytokine was injected in pyrogenic and subpyrogenic doses during 1 week (1, 2 or 3 weeks of life). The behavior was tested in the young (40-45 days) and adult (3 months) rats in the "open field" and "elevated plus maze". The greatest behavior disordes (elevation of act's number and of motor activity, the decrease of investigation activity) are revealed in the young animals treated with IL-Ib during 1 and 3 weeks of life. These behavioral changes were marked in rats injected with pyrogenic and subpyrogenic doses of cytokine. They had a similar tendency in male and female rats. At the age of 3 months, behavior changes revealed in juvenile rats were insignificant.     

Regulation of succinyl-CoA:3-oxoacid CoA-transferase in developing rat brain: responsiveness associated with prenatal but not postnatal hyperketonemia

Activities of ketone body-metabolizing enzymes in rat brain rise 3- to 5-fold during the suckling period, then fall more than 50% after weaning. Our purpose was to determine the mechanism of the developmental changes in activity of 3-oxoacid CoA-transferase in rat brain and to study its regulation by dietary modification. Purified rat brain 3-oxoacid CoA-transferase was used to generate specific antibody. Immunotitrations of the enzyme from brains of 4-, 24-, and 90-day-old rats indicated that changes in 3-oxoacid CoA-transferase activity during development are due to changes in content of the enzyme protein. Pulse-labeling studies showed that changes in enzyme specific activity reflected changes in its relative rate of synthesis, which increased 2.5-fold between the nineteenth day of gestation and the third postnatal day, remained at this high level until the twelfth postnatal day, and declined thereafter, returning by Day 38 to the level observed in utero. The enzyme is apparently degraded very slowly during early postnatal life. Fetal hyperketonemia induced by feeding pregnant rats a high-fat diet was associated with an increase in the relative rate of synthesis of 3-oxoacid CoA-transferase in brains of 19-day-old fetuses and newborn rats and with an increase in the specific activity of the enzyme at birth. To examine the role of postnatal hyperketonemia in the development of the enzyme in brains of suckling rats, neonates received intragastric cannulas and were fed, for up to 13 days, a modified milk formula low in fat. Postnatal hyperketonemia was abolished but cerebral 3-oxoacid CoA-transferase specific activity on Days 10 and 17 was not significantly affected. Thus, the physiological hyperketonemia caused by the high fat content of rat milk is not required for the normal development of 3-oxoacid CoA-transferase in rat brain.     

Ontogenic pattern of dopamine, acetylcholine, and acetylcholinesterase in the brains of normal and hypothyroid rats.

The influence of neonatal thyroidectomy (Tx) on developmental changes in dopamine (DA), acetylcholine (ACh), and acetylcholinesterase (AChE) was studied in the whole brain of rats. In control animals, brain levels of ACh gradually increased and attained adult values at the 70th day. In contrast, AChE activity showed a rapid increase between the 7th and 30th days. Levels of DA were low during the early postnatal life but markedly increased to reach adult values of 1.47 mug/g at the 30th day, after which no further enhancement was noted. Neonatal Tx interfered with the normal growth of the animals, decreased brain weights, and markedly influenced the developmental pattern of both DA and ACh in the brain. The concentration of DA in 30-day-old hypothyroid rats was 46% of the control values. In contrast, brain ACh levels in Tx rats were consistently above those seen in controls, being significantly higher, by 49 and 64%, at 15 and 30 days, respectively. Activity of AChE in brains of hypothyroid animals was not significantly different from that in controls. Treatment of Tx rats with thyroid hormone virtually restored the levels of DA and ACh to values in control animals.     

Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system.

The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum.     

Effect of excitotoxic lesions of the neonatal ventral hippocampus on the immobility response in rats

Rats with neonatal ventral hippocampal (nVH) lesions show postpubertal hypersensitivity to dopamine agonists, which may be reversed by neuroleptic treatment. In addition, the immobility response (IR) may be regulated by dopaminergic activity. We investigated the influence of the IR caused by clamping the neck of rats that had received bilateral ibotenic acid lesions of the ventral hippocampus at postnatal day 7 (PD7). At both ages, prepubertal (PD35) and postpubertal (PD56), the duration of the IR was significantly increased in animals with lesions when compared to controls. These findings indicate that nVH damage results in behavioral changes, such as enhancement of the IR, related to mesolimbic dopaminergic transmission.