Serotonin receptor binding and mRNA expression in the hippocampus of fearful amygdala-kindled rats

Amygdala kindling in rats increases fear behavior. The neural correlates of this fear are not well understood. In this experiment, we investigated the relation between serotonin receptor binding and mRNA expression and fearful behavior in amygdala-kindled rats. Rats received either 100 kindling stimulations or sham stimulations, and their fear behavior was subsequently assessed in an unfamiliar open field. Then, the rats were sacrificed and 5-HT transporter binding, 5-HT1A and 5-HT2A receptor binding, and 5-HT1A mRNA expression in several brain regions was assessed. The kindled rats were significantly more fearful in the open field than the sham-stimulated rats. They also had significantly more 5-HT1A receptor binding and mRNA expression in the dentate gyrus than the sham-simulated rats, and these increases in 5-HT1A receptor binding and mRNA expression were significantly correlated to the increases in fear. There were no significant differences between the kindled and sham-stimulated rats in 5-HT transporter binding or 5-HT2A receptor binding. These results suggest that alterations in 5-HT1A receptors in the dentate gyrus may play a role in the expression of kindled fear.     

Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats

The impairment of learning and memory is one of the most powerful and least understood effects of marijuana although the hippocampal formation appears to be one CNS region mediating these effects. We have shown that systemic injection of Delta9-tetrahydrocannabinol (THC), an active component of marijuana, impairs spatial learning more efficaciously in adolescent rats, compared with adult rats, but there have been no studies of the cellular mechanisms underlying this developmental sensitivity. In this study, we examined cannabinoid-mediated activity in hippocampal area CA1 neurons in brain slices from adolescent and adult rats. The magnitude of endocannabinoid-mediated synaptic functions such as long-term depression of inhibition was greater in the hippocampal slices from adolescent rats than in those from adults. The effect of R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazine-6-yl)(1-naphtalenyl) methanone mesylate (WIN55,212-2), an exogenous cannabinoid agonist, to suppress GABA(A) receptor-mediated synaptic responses was also greater in the hippocampal slices from adolescent rats than in those from adults. However, tonic endocannabinoid effects, shown as an increase of the spontaneous IPSC frequency by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a specific CB1 receptor antagonist, were greater in CA1 neurons from adult rats than in those from adolescent rats. On the other hand, WIN55,212-2 suppressed glutamate-mediated excitatory neurotransmission in CA1 pyramidal cells from adolescent and adult rats with similar efficacy. These results indicate that inhibitory synaptic function in the adolescent hippocampus is more sensitive to cannabinoid effects and may account, in part, for the greater sensitivity of adolescent animals to THC-induced memory impairment.     

Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons

In the present study, serotonin (5-HT) responses of hippocampal pyramidal cornu ammonis 1 (CA1) neurons were studied in rats subjected twice daily for 21 days to unpredictable stressors. In hippocampal tissue from thus stressed rats mRNA expression of the 5-HT(1A) receptor and mineralo- as well as glucocorticoid receptors were examined with in situ hybridization. On average, stressed rats displayed increased adrenal weight and attenuated body weight gain compared with controls, supporting that the animals had experienced increased corticosterone levels due to the stress exposure. One day after the last stressor, under conditions that corticosterone levels were low (predominant mineralocorticoid receptor activation), the 5-HT(1A) receptor mediated hyperpolarization of CA1 neurons in response to 10 microM 5-HT was significantly reduced compared with controls. Basal membrane properties of CA1 cells in stressed rats were comparable to those of controls. The 5-HT(1A) receptor mRNA expression was not changed after chronic stress exposure, in any of the hippocampal areas. A small but significant increase in mineralocorticoid receptor mRNA expression was observed after stress in the dentate gyrus, while glucocorticoid receptor expression was unchanged. The data indicate that unpredictable stress exposure for 3 weeks results in suppression of 5-HT(1A) receptor-mediated responses, possibly due to posttranslational modification of the receptor.     

Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington's disease transgenic mice

Early loss of CB1 receptors is a hallmark of human Huntington's disease. Data from rodent studies suggest that preservation and activation of CB1 receptors may be protective against disease progression. R6/1 transgenic mice are considered to be a model of early pathogenic changes in Huntington's disease. We have shown previously that levels of CB1 in R6/1 mice prior to the onset of motor symptoms (12 weeks of age) remain high enough to justify commencement of cannabinoid drug treatment. Eight weeks of daily treatment with the cannabinoid agonists HU210 (0.01 mg/kg) and Δ⁹-tetrahydrocannabinol (THC, 10.00 mg/kg), or the inhibitor of endocannabinoid metabolism URB597 (0.30 mg/kg), did not alter the progressive deterioration of performance observed in motor behavioural testing. HU210-treated R6/1 mice experienced a significant increase in seizure events suggesting that this therapy may lower the seizure threshold and cautioning against highly efficacious agonists as potential therapy in this disease. Molecular characterisation of brains at the end of the study showed that there were no significant effects of HU210 or THC treatment on the ligand binding of cannabinoid CB1, dopamine D1, D2, serotonin 5HT2A or GABA_A receptors, nor CB1 or fatty acid amide hydrolase (FAAH) mRNA expression in R6/1 mice. Intriguingly, a significant increase in the number of ubiquitinated aggregates was observed in the striatum with HU210 treatment, indicating an influence of CB1 on the disease process. Chronic URB597 treatment preserved CB1 receptors in the R6/1 striatum, suggesting that the manipulation of endocannabinoid levels warrants further exploration.     

Age-related changes of dopamine receptors in the rat hippocampus: a light microscope autoradiography study

Hippocampus is a brain region involved in learning and memory and is particularly sensitive to ageing. It is supplied with a dopaminergic innervation arising from the midbrain, which is part of the mesolimbic dopaminergic pathway. Dysfunction of the dopaminergic mesolimbic system is probably involved in the pathophysiology of psychosis and behavioural disturbances occurring in the elderly. The present study was designed to assess the density and localisation of dopamine D1- and D2-like receptor subtypes in the hippocampus of male Sprague-Dawley rats aged 3 months (young), 12 months (adult) and 24 months (old). Dopamine D1-like receptors, labelled by [3H]-SCH 23390, in young rats displayed a dentate gyrus-CA1 subfield gradient. The expression was increased in the cell body of dentate gyrus, CA4 and CA3 subfield of old rats compared to younger cohorts, as well as in the neuropil of dentate gyrus. A decreased density of dopamine D1-like receptors was found in the stratum oriens of CA1 and CA3 subfields. Dopamine D2-like receptors, labelled using [3H]-spiperone as radioligand, were expressed rather homogeneously throughout different subfields of the hippocampus. In old rats, the density of dopamine D2-like receptors was decreased in the dentate gyrus, unchanged in the CA4 and CA1 subfields and increased in the CA3 subfield. The above results indicate the occurrence of inhomogeneous changes in the density of dopamine D1- and D2-like receptors in specific portions of hippocampus of old rats. These findings support the hypothesis of an involvement of dopaminergic system in behavioural abnormalities or psychosis occurring in ageing.     

Ovarian hormone effects on 5-hydroxytryptamine(2A) and 5-hydroxytryptamine(2C) receptor mRNA expression in the ventral hippocampus and frontal cortex of female rats

Alterations in female gonadal hormones are associated with anxiety and mood changes. The aim of the present study was to determine influences of chronic gonadal hormone supplementation on 5-HT(2A) and 5-HT(2C) receptor mRNA levels in the ventral hippocampus and the frontal cerebral cortex. Ovariectomized adult female Sprague-Dawley rats (n=37) received implantation of subcutaneous pellets containing different dosages of 17beta-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels were analyzed by in situ hybridization in the ventral hippocampus and 5-HT(2A) receptor mRNA also in the frontal cortex. Estradiol treatment in combination with low-dose progesterone increased 5-HT(2A) receptor mRNA by 43% in the CA2 region of the ventral hippocampus, while estradiol combined with high-dose progesterone increased the expression of this gene by 84% in ventral CA1. 5-HT(2A) mRNA expression in the frontal cortex was not influenced by hormone manipulation. 5-HT(2C) receptor gene expression was in the ventral hippocampus decreased in the CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8-20% decreases). Effects on mood by gonadal hormones can be mediated, at least partly, through influences on 5-HT(2A) and 5-HT(2C) receptor expression.     

Repeated administration of a synthetic cannabinoid receptor agonist differentially affects cortical and accumbal neuronal morphology in adolescent and adult rats

Recent studies demonstrate a differential trajectory for cannabinoid receptor expression in cortical and sub-cortical brain areas across postnatal development. In the present study, we sought to investigate whether chronic systemic exposure to a synthetic cannabinoid receptor agonist causes morphological changes in the structure of dendrites and dendritic spines in adolescent and adult pyramidal neurons in the medial prefrontal cortex (mPFC) and medium spiny neurons (MSN) in the nucleus accumbens (Acb). Following systemic administration of WIN 55,212-2 in adolescent (PN 37–40) and adult (P55–60) male rats, the neuronal architecture of pyramidal neurons and MSN was assessed using Golgi–Cox staining. While no structural changes were observed in WIN 55,212-2-treated adolescent subjects compared to control, exposure to WIN 55,212-2 significantly increased dendritic length, spine density and the number of dendritic branches in pyramidal neurons in the mPFC of adult subjects when compared to control and adolescent subjects. In the Acb, WIN 55,212-2 exposure significantly decreased dendritic length and number of branches in adult rat subjects while no changes were observed in the adolescent groups. In contrast, spine density was significantly decreased in both the adult and adolescent groups in the Acb. To determine whether regional developmental morphological changes translated into behavioral differences, WIN 55,212-2-induced aversion was evaluated in both groups using a conditioned place preference paradigm. In adult rats, WIN 55,212-2 administration readily induced conditioned place aversion as previously described. In contrast, adolescent rats did not exhibit aversion following WIN 55,212-2 exposure in the behavioral paradigm. The present results show that synthetic cannabinoid administration differentially impacts cortical and sub-cortical neuronal morphology in adult compared to adolescent subjects. Such differences may underlie the disparate development effects of cannabinoids on behavior.     

复方丹参对脑缺血再灌注后大鼠海马和齿状回神经细胞凋亡及Bcl-2 mRNA表达的影响

目的:探讨中药复方丹参对大鼠脑缺血再灌注后海马和齿状回神经细胞凋亡及Bcl-2 mRNA表达的影响。方法:采用大脑中动脉内栓线法建立大鼠大脑中动脉缺血再灌注模型,应用原位细胞凋亡检测和原位杂交技术检测大鼠海马和齿状回神经细胞凋亡和Bcl-2 mRNA的表达并做图像分析。结果:与假手术对照组比较,缺血再灌注组凋亡神经细胞主要位于缺血侧海马CA1、CA3区,齿状回凋亡细胞较少。3个区神经细胞Bcl-2mRNA的表达在缺血再灌注2 h后升高,随时间的延长逐渐增强。复方丹参组神经细胞Bcl-2 mRNA的表达明显强于缺血再灌组,而凋亡神经细胞数明显较低。结论:复方丹参可通过上调神经细胞Bcl-2 mRNA的表达,抑制神经细胞凋亡,从而减轻缺血再灌注对大鼠海马和齿状回的损伤。     

Lack of response suppression follows repeated ventral tegmental cannabinoid administration: an in vitro electrophysiological study

Cannabinoid compounds have been reported to excite ventral tegmental neurons through activation of cannabinoid CB1 receptors. More recently, biochemical and whole-cell voltage-clamp studies carried out on CB1-transfected AtT20 cells have shown a rapid desensitization of these receptors following activation of protein kinase C by 4-alpha-phorbol. To investigate the possible physiological correlates of this phenomenon, we have studied the effects of repeated cannabinoid treatment on ventral tegmental area dopaminergic neuronal firing in vitro. Rat brain slices containing the ventral tegmental area were used for single-unit extracellular recordings. Only neurons meeting established electrophysiological and pharmacological criteria for dopaminergic neurons were used in the study (firing neurons were detected either using tungsten or glass microelectrodes). The high-affinity cannabinoid agonist HU210 produced a concentration-dependent increase in firing (1-15 microM; EC(50) approximately 7 microM). Initial HU210 exposure produced a significant increase in cell firing rate in the ventral tegmental area, with a maximum approximately 3.5-fold increase over pre-drug basal firing; a subsequent exposure to HU210 produced an approximately threefold increase over basal firing. Nevertheless, the duration and onset of excitation produced by the cannabinoid differed significantly between the first and second exposures; the first excitation lasted significantly longer than the second and required less time to reach a comparable change in firing rate. The increases in firing rate and the time to return to basal firing were not significantly different between exposures. Furthermore, the cannabinoid antagonist SR141716A completely prevented the HU210-induced excitation whilst having no effect on its own, thus indicating a CB1-receptor mediated mechanism for the observed increase in firing. Ventral tegmental area neurons are also excited by the GABA(A) receptor antagonist bicuculline. To assess the role of GABA in cannabinoid-mediated excitation, HU210 was added in the presence of bicuculline. HU210 did not affect the initial bicuculline-induced increase in firing, suggesting different sites of action for the two compounds.Our data fail to support previously reported findings using repeated cannabinoid administration and cell preparations. The maintained increase in DA drive elicited by the potent cannabinoid agonist HU210 in the in vitro ventral tegmental circuit could explain some of the behavioural properties of cannabinoids, such as the lack of tolerance for the psychotropic effects of marijuana seen in human users.     

The effects of antipsychotic drugs administration on 5-HT1A receptor expression in the limbic system of the rat brain

Increasing evidence suggests that 5-HT1A receptors are involved in the pathophysiology and treatment of schizophrenia. This paper investigated 5-HT1A receptor mRNA expression and binding density in female rats treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (control) orally three times/day for 1 or 12 weeks. Animals were sacrificed 48 h after the last administration. Aripiprazole significantly increased 5-HT1A receptor binding density by 33% in the CA1 region of the hippocampus and by 21% in the medial posterodorsal nuclei of posterior amygdala (MeP) compared to the control group after 1 week of treatment. Olanzapine significantly decreased 5-HT1A receptor binding density by 17–22% in Layers I–IV of the cingulate cortex after 1 week of treatment. Neither of these antipsychotic drugs affected 5-HT1A receptor binding density after 12 weeks drug treatment. As expected, haloperidol treatment did not have any significant effect on 5-HT1A binding density after 1 or 12 weeks of treatment. 5-HT1A receptor mRNA expression was not altered by antipsychotic treatment in any brain region. The results indicate that aripiprazole and olanzapine have differential effects on 5-HT1A receptor expression, which may contribute to their distinct profiles in improving negative symptoms and cognitive deficits in schizophrenia. Aripiprazole and olanzapine may produce adaptation and desensitization of 5-HT1A receptor expression after long term treatment.     

Benzodiazepine-mediated regulation of alpha1, alpha2, beta1-3 and gamma2 GABA(A) receptor subunit proteins in the rat brain hippocampus and cortex.

Prolonged flurazepam exposure regulates the expression of selected (alpha1, beta2, beta3) GABA(A) receptor subunit messenger RNAs in specific regions of the hippocampus and cortex with a time-course consistent with benzodiazepine tolerance both in vivo and in vitro. In this report, the immunostaining density of six specific GABA(A) receptor subunit (alpha1, beta2, beta1-3 and gamma2) antibodies was measured in the hippocampus and cortex, among other brain areas, in slide-mounted brain sections from flurazepam-treated and control rats using quantitative computer-assisted image analysis techniques. In parallel with the localized reduction in alpha1 and beta3 subunit messenger RNA expression detected in a previous study, relative alpha1 and beta3 subunit antibody immunostaining density was significantly decreased in flurazepam-treated rat hippocampal CA1, CA3 and dentate dendritic regions, and in specific cortical layers. Quantitative western blot analysis showed that beta3 subunit protein levels in crude homogenates of the hippocampal dentate region from flurazepam-treated rats, an area which showed fairly uniform decreases in beta3 subunit immunostaining (16-21%), were reduced to a similar degree (18%). The latter findings provide independent support that relative immunostaining density may provide an accurate estimate of protein levels. Consistent with the absence of the regulation of their respective messenger RNAs immediately after ending flurazepam administration, no changes in the density of alpha2, beta1 or beta2 subunit antibody immunostaining were found in any brain region. gamma2 subunit antibody staining was changed only in the dentate molecular layer. The selective changes in GABA(A) receptor subunit antibody immunostaining density in the hippocampus suggested that a change in the composition of GABA(A) receptors involving specific subunits (alpha1 and beta3) may be one mechanism underlying benzodiazepine anticonvulsant tolerance.     

Role of serotonin in the regulation of the dynorphinergic system by a kappa-opioid agonist and cocaine treatment in rat CNS

It has been shown that chronic cocaine increases prodynorphin mRNA in the caudate putamen and decreases it in the hypothalamus. In addition, treatment with a kappa-opioid receptor agonist produced the opposite effect on prodynorphin gene expression in these brain regions and also evoked a decrease in the hippocampus. It is already known that kappa-opioid receptor agonists decrease the development of sensitization to some of the behavioral effects of cocaine. The serotonin system has also been shown to regulate dynorphin gene expression and a continuous infusion of fluoxetine induced prodynorphin gene expression in the same pattern as the kappa-opioid agonist (+)(5a,7a,8b)-N-methyl-N-[7-(1-pyrrolidinyl)-1 oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) in the brain regions investigated. It is interesting to note that treatment with a continuous infusion of cocaine produced different effects on this parameter. To determine whether serotonin plays a role in the regulation of prodynorphin mRNA by kappa-opioid agonists or cocaine, rats were treated with the serotonin depleter parachloroamphetamine (PCA). Beginning 24 h later, rats were treated with the selective kappa-opioid agonist U-69593 for 5 days or continuously with cocaine for 7 days and prodynorphin mRNA was measured. Prodynorphin mRNA was decreased significantly in the hypothalamus, caudate putamen, and hippocampus of rats treated with a single injection of PCA. Subsequent to PCA administration the effects of U-69593 or cocaine on prodynorphin mRNA were differentially affected across brain regions. Prodynorphin gene expression was still increased by U-69593 treatment in the hypothalamus and decreased in the caudate putamen. Cocaine treatment still produced a decrease in this parameter in the hypothalamus and an increase in the caudate putamen. In contrast, in the hippocampus, the decrease in prodynorphin mRNA produced by U-69593 was no longer evident after PCA and cocaine, which previously had no effect, now increased it in the serotonin-depleted group. These findings suggest that serotonin is necessary to maintain normal levels of dynorphin mRNA in all of the investigated brain areas and that the regulation of prodynorphin mRNA expression by chronic treatment with a kappa-opioid receptor agonist or cocaine requires serotonin in the hippocampus, but not in the hypothalamus or caudate putamen.     

Quantified distribution of the serotonin innervation in adult rat hippocampus

To quantify the serotonin innervation in adult rat hippocampus, serotonin axon terminals (varicosities) were uptake-labeled for light microscope radioautography in whole hemisphere slices incubated with 1 microM [3H]serotonin. The labeled varicosities were visualized as small aggregates of silver grains and counted with the aid of an image analysis system across all layers in representative sectors of subiculum, Ammon's horn (CA1, CA3-a, CA3-b) and dentate gyrus (medial blade, crest and lateral blade). Counts were obtained in six rats at three equidistant horizontal levels from the ventral two-thirds of the hippocampus. After double correction for duration of radioautographic exposure and section thickness, and measurement of the mean diameter of labeled varicosities in electron microscope radioautographs, the results were expressed in number of varicosities per mm3 of tissue. The overall density of hippocampal serotonin innervation was thus evaluated at 2.7 x 10(6) varicosities per mm3, and appeared significantly higher in subiculum (3.6 x 10(6)) and Ammon's horn (3.1 x 10(6)) than in dentate gyrus (2.2 x 10(6)). Subiculum and dentate gyrus-crest (2.0 x 10(6)) had the highest and lowest regional densities. There was a marked heterogeneity also in terms of laminar distribution. For example, the stratum moleculare of subiculum and CA1, and the stratum oriens of CA3 (5.2 x 10(6)) varicosities in CA3-a), showed much higher values than the pyramidal cell layer (0.7, 1.1 and 0.7 x 10(6) in CA1, CA3-a and CA3-b, respectively). Similarly, the granular layer of dentate gyrus had a much lower density (1.1 x 10(6)) than did the molecular (2.8 x 10(6)) and the polymorph layer (2.4 x 10(6)). From these data, it was possible to evaluate the mean endogenous amine content per hippocampal serotonin varicosity (0.05-0.07 fg), and the average number of serotonin varicosities per hippocampal neuron in both CA3 (130) and dentate gyrus (20-35). In the context of current data on the distribution of serotonin receptors and diverse actions of serotonin at the cellular level in hippocampus, such quantified information provides new insights on some basic properties of serotonin in this part of the brain.     

Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain

The cannabinoid receptor one (CB1) is responsible for the effects of cannabis on motor and cognitive function in the CNS. There is to date very limited information about the CB1 gene expression in the human brain, in particular during fetal development. In the present study, in situ hybridization experiments were used to examine the microscopic and macroscopic organization of the CB1 mRNA expression in normal human fetal (approximately 20 weeks of development) and adult brains. The fetal brain showed a distinct heterogeneous pattern of the CB1 mRNA expression which was low to moderate in many brain areas. The most striking feature of the fetal brain was the intense expression in the hippocampal CA region and basal nuclear group of the amygdaloid complex. Many of the same brain areas that showed positive expression of the CB1 mRNA in the fetal brain also expressed the gene in the adult brain. However, aside from an intense expression in the hippocampus which resembled that in fetal brain, the adult brain showed very high expression throughout the cerebral cortex, caudate nucleus, putamen and cerebellar cortex. These results document a different pattern of the anatomical organization of the CB1 mRNA expression in the mid-gestation fetal and adult human brain. Overall, the high CB1 mRNA expression in the fetal hippocampus and amygdala indicates that these limbic structures might be most vulnerable to prenatal cannabis exposure.     

Serotonin receptor 5-HT5A in rat hippocampus decrease by leptin treatment

5-Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse receptors subtypes. In this work we studied the changes on the expression of 5-HT_5A receptors in rat hippocampus induced by leptin, an adipocyte-derived hormone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT_5A receptor gene expression a qRT-PCR was used and the distribution of those receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and leptin + serotonin treated. The results showed that even though the 5-HT_5A gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT_5A serotonin receptor decreased significantly in the dentate gyrus.     

Effects of status epilepticus on hippocampal GABAA receptors are age-dependent

Long-term GABA(A) receptor alterations occur in hippocampal dentate granule neurons of rats that develop epilepsy after status epilepticus in adulthood. Hippocampal GABA(A) receptor expression undergoes marked reorganization during the postnatal period, however, and the effects of neonatal status epilepticus on subsequent GABA(A) receptor development are unknown. In the current study, we utilize single cell electrophysiology and antisense mRNA amplification to determine the effect of status-epilepticus induced by lithium-pilocarpine in postnatal day 10 rat pups on GABA(A) receptor subunit expression and function in hippocampal dentate granule neurons. We find that rats subjected to lithium-pilocarpine-induced status epilepticus at postnatal day 10 show long-term GABA(A) receptor changes including a two-fold increase in alpha1 subunit expression (compared with lithium-injected controls) and enhanced type I benzodiazepine augmentation that are opposite of those seen after status epilepticus in adulthood and may serve to enhance dentate gyrus inhibition. Further, unlike adult rats, postnatal day 10 rats subjected to status epilepticus do not become epileptic. These findings suggest age-dependent differences in the effects of status epilepticus on hippocampal GABA(A) receptors that could contribute to the selective resistance of the immature brain to epileptogenesis.