Effects of reversible inactivation of the neonatal ventral hippocampus on behavior in the adult rat (original) (raw)
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Neuropsychopharmacology, 1993
The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implications of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these
Developmental Brain Research, 2005
Early destruction of the ventral hippocampus from postnatal day 7 (P7) has been shown to induce behavioral alterations in post-pubertal rats, similar to those observed in models for schizophrenia. Using a single injection of tetanus toxin into the ventral hippocampus at P1, we tested the consequences of an early neonatal activity deprivation (bP7) on behavioral and neurochemical parameters of pre-and post-pubertal rats. We found no significant differences in either behavioral or biochemical pattern, indicating that an early neonate neural activity blockade does not induce behavioral alterations in pre-and post-puberty rats. D 2005 Elsevier B.V. All rights reserved.
Cognitive Effects of Neonatal Hippocampal Lesions in a Rat Model of Schizophrenia
Neuropsychopharmacology, 1996
Lesioning the ventral hippocampus of neonatal rats has been proposed as an experimental model of schizophrenia. This lesion causes a syndrome of hyperresponsivity to the stimulant effects of amphetamine, impaired grooming and disrupted social interactions, effects that emerge during adolescence, much like schizophrenia. Persisting cognitive effects of neonatal ventral hippocampal lesions were assessed in the current study, because the hippocampus is critically important far a variety of cognitive functions and cognitive impairment and because it is an important feature of schizophrenia. Spatial learning and working memory were assessed in the radial-arm maze, which is sensitive to the adverse effects of hippocampal lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. Deficits were seen during the prepubertal period as well as in adulthood. Even though the lesioned rats performed mare poorly, they were significantly less sensitive to the amnestic
Behavioral Neuroscience, 2008
This research examined cognitive and motivational processes at different developmental stages in rats with neonatal ventral hippocampus (VH) lesions, an approach used to model schizophrenia. In Experiment 1, performance in a T-maze alternation task was assessed on postnatal days (PNDs) 22 and 23. VH-lesioned rats displayed a severe deficit relative to controls. In Experiment 2, behaviorally naive rats were tested for spontaneous alternation at PND 29. Alternation was intact in VH-lesioned rats only when successive alternations were separated by Ͼ5 s. In Experiment 3, motivation was tested in a cost-benefit T-maze task and in a saccharine-water preference test. Between PNDs 22-37, behaviorally naive rats with neonatal VH lesions displayed weaker saccharine preference than controls, but the 2 groups did not differ on the cost-benefit task. At adulthood, between PNDs 56-72, the difference on saccharine preference persisted and an impairment on the cost-benefit task emerged. Overall, these results suggest that working memory deficits observed at the weaning stage were not secondary to spontaneous alternation or motivation dysfunctions.
Neuroscience, 2006
This experiment assessed the effect of neonatal ventral hippocampus lesions in rats, a heuristic approach to model schizophrenia, on continuous delayed alternation and conditional discrimination learning performance before and after complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the tasks to help dissociate between a hippocampal and a prefrontal cortex dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral microinjections of ibotenic acid or phosphate-buffered saline in the ventral hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination task where a stimulus and a response location had to be paired. Deficits in ventral hippocampus-lesioned rats were observed in both tasks whether a delay was introduced before a response or not. Impaired performance regardless of delay length, combined with high rates of perseverative errors, suggested a ...
Neuropsychopharmacology, 2011
These experiments determined the mesolimbic modulation of cortical cholinergic transmission in a neurodevelopmental model of schizophrenia. Mesolimbic-cholinergic abnormalities are hypothesized to contribute to the cognitive deficits seen in schizophrenia. Stimulation of NMDA receptors in nucleus accumbens (NAC) increases acetylcholine (ACh) release in the prefrontal cortex (PFC), a mechanism recently demonstrated to contribute to the control of attentional performance. We determined the ability of intra-NAC administration of NMDA to increase prefrontal ACh levels in adult rats that had received bilateral infusions of tetrodotoxin (TTX) to transiently interrupt impulse flow in the ventral hippocampus (VH) during development. Rats received infusions of TTX or saline on postnatal day 7 (PD7) or day 32 (PD32), and the effects of NAC NMDA receptor stimulation on prefrontal cholinergic neurotransmission were assessed in adulthood. In animals treated as controls on PD7, NMDA increased prefrontal ACh levels by 121% above baseline. In contrast, PD7 infusions of TTX into the VH abolished the ability of NAC NMDA to activate prefrontal cholinergic neurotransmission (7% increase). In animals that received TTX infusions on PD32, NMDA-evoked cholinergic activity did not differ from controls, indicating a restricted, neonatal critical period during which VH TTX impacts the organization of mesolimbic-basal forebrain-cortical circuitry. Importantly, the failure of NAC NMDA to evoke cholinergic activity in rats treated with TTX on PD7 did not reflect a reduced excitability of corticopetal cholinergic neurons because administration of amphetamine produced similar elevations of prefrontal ACh levels in PD7 TTX and PD7 control animals. A third series of experiments demonstrated that the effects of PD7 TTX are a specific consequence of transient disruption of impulse flow in the VH. Intra-NAC NMDA evoked prefrontal ACh release in rats receiving TTX, on PD7, into the dorsal hippocampus (DH), basolateral amygdala, or NAC. Thus, impulse flow specifically within the VH, during a sensitive period of development, is necessary for the functional organization of a mesolimbic-cortical circuit known to mediate attentional control processes. Therefore, neonatal inactivation of VH represents an effective animal model for studying the basis of certain cognitive symptoms of schizophrenia.
Synapse, 2005
The neonatal ventral hippocampal (nVH) and the neonatal prefrontal cortex (nPFC) lesions in rats have been used as models to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. We investigated the role of the nVH and the nPFC lesions on behavioral characteristics related to locomotor behaviors, social interaction, and grooming. Bilateral ibotenic acid lesions of the VH, the PFC, or both were made in neonatal Sprague-Dawley rats (postnatal day 7, P7) and their behaviors studied at P35 and P60. No significant differences in any of the behaviors were observed between sham animals and rats with ibotenic acid lesions at P35. Postpubertally (at P60), the spontaneous locomotor activity of nVH-lesioned rats was significantly enhanced compared to the sham controls; however, this hyperactivity was reversed by nVH and nPFC double lesions. Neonatal PFC lesion alone did not alter spontaneous activity, although a trend of increased activity was observed. The duration of grooming was significantly decreased in rats with neonatal lesions of the VH. Similar to the data on locomotion, nVH plus nPFC lesion normalized the grooming behavior. Lesion of the PFC alone was without any significant effect on grooming behavior. Neonatal VH-lesioned animals spent less time in active social interaction, and this effect persisted even in nVH plus nPFC-lesioned animals. By itself, nPFC lesion did not alter social behavior. These data suggest that subtle developmental aberrations within PFC caused by nVH lesions, rather than the lesion of PFC itself, may contribute to some of the behavioral changes seen in the nVH-lesioned rats.
Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats
2012
A neonatal ventral hippocampal lesion (NVHL) in rats has been commonly used as a neurodevelopmental model to mimic schizophrenia-like behaviors. Recently, we reported that NVHL resulted in dendritic retraction and spine loss in pyramidal neurons of the prefrontal cortex (PFC). In addition, the hippocampus and PFC are important structures in the regulation of the electroencephalographic (EEG) activity. Patients with PFC lesions show deficits in the EEG activity. This study aimed to determine whether the EEG activity was altered in NVHL rats. In addition, we also analyzed the locomotor activity induced by a novel environment and exploratory behavior using the hole-board test. Consistent with the behavioral findings, the EEG analysis of the cortical regions showed that the NVHL rats displayed a lower power in cortical bands. At 1-8 Hz, 9-14 Hz, and 15-30 Hz bands, our findings showed a decrease in the absolute power of the parietal and occipital cortices recordings. In addition, the NVHL rats also showed a reduction in the exploratory behavior tested using the hole-board test. In conclusion, this study demonstrated that the EEG activity was reduced in adult NVHL rats and suggests that this may play a role in the behavioral changes observed in this neurodevelopmental model of schizophrenia. Synapse 66:738-746, 2012. V V C 2012 Wiley Periodicals, Inc.
Epilepsy Research, 2017
Prenatal stress and drug exposure induce permanent alterations of the brain. Even though different brain structures are involved, alterations almost always refer to the hippocampus. The aim of this study was to investigate the excitability of hippocampal slices in low-magnesium epilepsy model of prenatally methamphetamine (MA, 5 mg/kg sc.) or saline (sc., stress model) exposed animals in adult male rats. The second aim was to investigate, if a low dose of MA (1 ml/kg s.c.) administered in adulthood changes the hippocampal activity of these animals. Adult Wistar male rats were divided into groups according to their prenatal treatment (C − naïve control; Sa − saline; MA − MA administration). One half of the animals was treated with a challenge dose of MA (1 mg/kg sc.) 45 min before hippocampal slices were cut. The activity of 350 μ thick transversal slices of CA1 hippocampi was recorded (latencies of the first epileptiform discharge and the regular epileptiform activity) and evaluated in ACSF with low-magnesium concentration. Effects of prenatal exposure: The highest excitability was found in the Sa (prenatally stressed) group in respect to C and MA groups. This group developed also the highest number of seizure-like events. In addition, the prenatally MA treated group had also higher excitability than C group. Effects of the MA challenge dose: The challenge dose decreased the excitability of prenatally SA-exposed group. To conclude, even a mild prenatal stress significantly increases hippocampal excitability in adulthood and a challenge dose of MA is able to dampen it.