Cerebral palsy rates among low-birthweight infants fell in the 1990s

Using a population-based register, this study sought to ascertain changes in the rate and severity of cerebral palsy (CP) in a geographically defined area of the UK among infants weighing less than 1500 g and born between 1984 and 1995. There were 417414 live births in the area, which included Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. Of the 898 children with CP (526 males, 372 females), 194 (21.6%) weighed less than 1500 g at birth. The overall CP rate for neonatal survivors fell from 2.5 out of every 1000 in 1984 to 1986 to 1.7 in 1993 to 1995. The rate for those weighing less than 1000 g rose to 90 out of every 1000 neonatal survivors in 1987 to 1989 and then fell to 57 in 1993 to 1995. A similar pattern is seen among infants weighing 1000 to 1499 g at birth, the rate rising to 77 in 1987 to 1988 and then falling to 40 in 1993 to 1995. The rate of severe motor disability among infants weighing less than 1500 g also decreased (24.6 in 1984-1986 to 12.5 in 1993-1995). The relation of these findings to changes in perinatal care in the early 1990s is not known.     

Genetics of frontotemporal dementia and alterations of the tau gene

The prevalence of fronto-temporal dementia may be estimated in 10-20% of all dementia's. In 40 to 50% of the cases it is possible to detect familial antecedents and in some of the families it is possible to identify multiple affected individuals. The study of these familial cases has allowed to narrow the responsible genomic region to chromosome 17 and to identify mutations in the tau gene as responsible for the disease. At present more than 100 cases of the disease due to mutations in the tau gene have been described in which it has been possible to detect 24 different mutations. In order to search for mutations in the tau gene in a patient all it is needed is a sample of venous blood with which it is possible to extract the genomic DNA, amplify the tau gene through PCR and to sequence it. The information obtained provides a very precise diagnosis in patients with fronto-temporal dementia, may be useful in the differential diagnosis with other types of dementia, and may allow a pre-symptomatic diagnosis in relatives from patients. At a more basic level, the detection of mutations in the tau gene allows to identify the pathogenic mechanisms involved opening up the possibility to develop new therapeutics strategies.     

Altered expression of antithrombotic molecules in human glioma vessels

A total of 14 surgical specimens, including 7 glioblastomas, 3 anaplastic astrocytomas, 2 brains adjacent to glioblastoma and 2 grossly normal brains, were investigated immunohistochemically for the expression of antithrombin III (AT-III), heparan sulfate proteoglycan (HSPG) and thrombomodulin (TM) in the endothelium of microvessels. The immunoreaction to AT-III was of moderate intensity in grossly normal brains, brains adjacent to glioblastoma, and anaplastic astrocytomas, but was only weak in glioblastomas, especially in the capillaries. The immunoreaction to HSPG was constantly intense in the microvessels in all the specimens. Although the immunoreaction to TM was negative or only faint in the microvessels in grossly normal brains, it was moderately to strongly intense in anaplastic astrocytomas and brains adjacent to glioblastoma. The intensity of immunoreaction to TM was variable, from faint to strong in the capillaries, and moderate to strong in larger microvessels in glioblastomas. The present study suggested that the alterations in the expression of those antithrombotic molecules could explain, at least in part, the tendencies for intratumoral hemorrhage as well as intravascular thrombosis in the different areas of malignant gliomas.Supported in part by the Grant-in-Aid for Cancer Research (4-23) from the Japanese Ministry of Health and Welfare     

Cardiovascular responses to electrical stimulation of the ventrolateral medulla of the spontaneously hypertensive rat

Cardiovascular responses to electrical microstimulation of the ventrolateral medulla were investigated in both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) under pentobarbital anesthesia. The threshold intensity required to elicit a change in blood pressure (BP) and the cardiovascular responses in these two groups of rats upon electrical stimulation were compared. It was found that the region with the lowest threshold intensities was located in the rostral ventrolateral medulla (RVL) and the threshold intensities were much lower in SHR than in WKY. Electrical stimulation of this brain region also resulted in a greater increase in BP during stimulation in SHR, compared to control. In SHR, upon termination of stimulation, the BP dropped to a level above the pre-stimulation level and this was followed by a prolonged, sustained elevation in BP before returning to the control level, whereas in WKY, the BP showed an initial drop to below the pre-stimulation level and then returned to the control level. These results suggest an enhanced responsiveness to electrical stimulation in SHR. Although the heart rate (HR) increased to a similar extent during electrical stimulation in both groups of rats, upon termination of stimulation WKY exhibited bradycardia followed by tachycardia before the HR returned to the pre-stimulation level, whereas SHR exhibited tachycardia which was maintained for a substantial period of time before returning to the pre-stimulation level. The results suggest a lower baroreceptor sensitivity in SHR. The change in HR/change in BP was smaller in SHR than in WKY, suggesting that the increase in HR may not contribute to the increase in BP during stimulation as much in SHR as in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cognitive evoked potentials in narcolepsy: a review of the literature

Subtle cognitive deficits have been described in narcolepsy. They have been hypothesised to be related to changes in the hypocretin system. Event-related potential (ERP) paradigms are known to be useful tools in the investigation of information processing and seem to be sensitive to subtle neuropsychological changes. We review empirical articles on ERPs in narcolepsy in order to contribute to clarify the pattern of cognitive deficits that are specific to this disease and, possibly, to identify specific cognitive domains that improve with treatment. Fourteen peer-reviewed articles were selected for this review. These studies were conducted with passive and active oddball paradigms and support the existence of changes in cognitive attentive processing in narcolepsy, possibly in association with altered functioning of the prefrontal cortex. ERP low-resolution electromagnetic tomography revealed that modafinil improved information processing speed and increased energetic resources in prefrontal cortical areas. These findings suggest that it is worthwhile to further evaluate the usefulness of ERPs in the detection of cognitive dysfunction in this disorder before and after treatment.     

Electrical stimulation of the substantia nigra does not increase tail-flick latency in the rat

The effect of electrical stimulation at multiple sites in the midbrain was investigated in rats lightly anesthetized with barbiturate. The application of monopolar electrical stimulation to the substantia nigra (SN) or the adjacent cerebral peduncle failed to produce an elevation in tail-flick latency (TFL) in response to the application of noxious radiant heat. However, the same intensity of stimulation when applied to an area dorsal to the SN led to an elevation in TFL. This effect was not due to current spread to dopaminergic neurons in the zona compacta compartment of the SN because administration of cis-flupenthixol failed to block the effect. We conclude that, contrary to previous suggestions, discrete electrical stimulation of the SN itself does not give rise to a state of antinociception.     

The overall pattern of ocular dominance bands in cat visual cortex

This study describes the overall arrangement of geniculocortical input representing the system of cortical ocular dominance bands in layer IV of striate cortex in the adult cat. The pattern of ocular dominance bands was revealed by transneuronal transport of the intraocularly injected tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Our data indicate that this procedure does not damage the retina and that it results in relatively uniform uptake and transport of the tracer. Using previously published techniques (Olavarria and Van Sluyters, 1983, 1985), both cortical hemispheres of each cat were unfolded, flattened and tangentially sectioned. Analysis of the WGA-HRP labeling patterns in these sections revealed a relatively continuous network of irregularly branching bands in layer IV of area 17 in both hemispheres. Because of a systematic difference in the level of interband labeling, ocular dominance bands appear less distinct in the hemisphere contralateral to the injected eye. There is also a tendency for interband labeling to be greater in cortical regions that represent the more peripheral aspects of the binocular portion of the visual field. The width of an individual ocular dominance band in the cat fluctuates, so that it appears to be made up of a series of uniformly sized, roughly circular beads of label. The diameter of these beads averages 667 micron, and preliminary counts indicate that there are 650-675 beads in each striate cortex. Contrary to earlier suggestions, in 4 out of 6 hemispheres analyzed quantitatively there was no tendency for ocular dominance bands to be oriented along a preferred axis in cat striate cortex, including an axis orthogonal to the border between areas 17 and 18. Ocular dominance bands in area 18 appear to be broader than those in area 17, and they seem to have a greater tendency to be oriented orthogonal to the 17/18 border than those in area 17. Compared with the ocular dominance pattern in monkey striate cortex, the ocular dominance pattern in the cat is much less regular. In general, cat ocular dominance bands appear to fluctuate more in width, to change direction more often, and to be less likely to run orthogonal to the 17/18 border. The greater regularity of the primate ocular dominance pattern may be related to differences in the way in which the visual hemifield is mapped onto the striate cortex in these 2 species.     

Cardiac vagal responsiveness during development in spontaneously hypertensive rats

In the present study we sought to determine the effect of age, hypertension and endogenous angiotensin on the chronotropic responses to vagal stimulation in urethane anesthetized-normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). After beta-adrenoceptor blockade with atenolol, the right and left vagal nerves were stimulated with graded frequencies between 1 and 32 Hz in 5-, 8- and 22-week-old animals. At all ages and in both strains, there was a strong linear relationship between the degree of bradycardia and the log of the stimulation frequency. At the age of 5 weeks, the bradycardia to stimulation of the right vagus was greater in SHR than that observed in WKY (P<0.05). However, in 8- and 22 week-old animals, no differences were observed between the response to vagal stimulation in WKY and SHR. Thus, there was an age-dependent increase in the response to right vagal stimulation in WKY, but no such trend in SHR. No significant age-dependent changes in left vagal responses were observed in either strain. Left vagal responses were approximately half of the response to right vagal stimulation at all ages in SHR and in 8-22 week WKY, but similar to right vagal responses in 5 week WKY. Administration of the angiotensin converting enzyme inhibitor perindopril, which effectively blocked the formation of endogenous angiotensin, did not affect responses to vagal stimulation at any age, in either strain. These results suggest that the baroreflex vagal deficit observed in adult SHR compared to WKY is not due to a difference in the responsiveness of the cardiac vagal neuroeffector mechanism nor due to an effect of circulating angiotensin II. Furthermore, the enhanced vagal bradycardia observed in very young SHR which was due primarily to the earlier establishment of the adult vagal response pattern may indicate accelerated vagal development in this strain compared to WKY.     

Effective connectivity of a reward network in obese women

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.     

Le psychiatre aux urgences médico-judiciaires

The role of psychiatrists in Forensic Psychiatry Units is to assess: victims of crimes at the request of the Court in order to produce a medical certificate stating the psychological impact and determine the total inability to work; persons detainees in police custody, in order to allow the continuation of the custody. Although these missions are of a forensic nature, psychiatrists use this time to provide care to victims and to persons in custody.     

Very mild stress of pregnant rats reduces volume and cell number in nucleus accumbens of adult offspring: some parallels to schizophrenia

Pregnant rats subjected to very mild stress give birth to pups who, when examined as adults, exhibited behavioral and anatomical anomalies that resemble some aspects of schizophrenia. The nucleus accumbens (NAcc) is reduced in volume by 20.7 +/- 3.4% (p = 0.003) in pups born to mothers who were stressed during pregnancy by injections of either saline or amphetamine in saline. The total number of cells is decreased in proportion to the reduction in volume, so the volume cell density of the NAcc is not changed with treatment. The affected volume is localized in the ventral rostral area of the NAcc. Both males and females are affected, but males are slightly more sensitive to the challenge to the mother. Rats born to mothers stressed in mid-pregnancy appear to provide useful parallels to the fetal developmental hypothesis of schizophrenia and to the brain abnormalities seen in this disease.     

Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei

The cochlear nuclear complex gives rise to widespread projections to nuclei throughout the brainstem. The projections arise from separate, well-defined populations of cells. None of the cell populations in the cochlear nucleus projects to all brainstem targets, and none of the targets receives inputs from all cell types. The projections of nine distinguishable cell types in the cochlear nucleus—seven in the ventral cochlear nucleus and two in the dorsal cochlear nucleus—are described in this review. Globular bushy cells and two types of spherical bushy cells project to nuclei in the superior olivary complex that play roles in sound localization based on binaural cues. Octopus cells convey precisely timed information to nuclei in the superior olivary complex and lateral lemniscus that, in turn, send inhibitory input to the inferior colliculus. Cochlear root neurons send widespread projections to areas of the reticular formation involved in startle reflexes and autonomic functions. Type I multipolar cells may encode complex features of natural stimuli and send excitatory projections directly to the inferior colliculus. Type II multipolar cells send inhibitory projections to the contralateral cochlear nuclei. Fusiform cells in the dorsal cochlear nucleus appear to be important for the localization of sounds based on spectral cues and send direct excitatory projections to the inferior colliculus. Giant cells in the dorsal cochlear nucleus also project directly to the inferior colliculus; some of them may convey inhibitory inputs to the contralateral cochlear nucleus as well.     

The vestibular nuclei in the domestic hen (Gallus domesticus). IV. The projection to the spinal cord

Horseradish peroxidase was injected at various levels of the spinal cord of the hen and the cells in the brain stem, labeled due to retrograde transport of the tracer enzyme, were mapped with particular reference to the vestibular nuclear complex. The Deiters' nuclei project ipsilaterally to the spinal cord. The projection from the nucleus Deiters ventralis reaches down to the lumbosacral spinal cord. The spinal projection from the nucleus Deiters dorsalis is somatotopically organized. Cells localized rostrally within the nucleus project to upper parts of the spinal cord cells localized caudally project to the lumbosacral spinal cord. The medial and the descending nucleus contain labeled cells in two compartments of the nuclei. In each of them a rostral one projects to the upper cervical cord, a caudal one projects to the thoracical spinal cord. In addition, labeled cells are observed in the reticular formation, mainly in the pons and the medulla oblongata, in the red nucleus, in the raphe nuclei and in the periaqueductal grey. Very few labeled cells are observed in the locus ceruleus, the nucleus intercalatus and in the nucleus of the solitary tract. In some cases, the number of labeled cells in the various nuclei in the brain stem projecting to the spinal cord was counted to get an impression of the quantitative importance of the vestibulospinal projection relative to afferents to the spinal cord from the other nuclei. The findings are discussed in the light of what is known of the vestibulospinal projection in mammals.     

Nucleus z in the rat: spinal afferents from collaterals of dorsal spinocerebellar tract neurons

Proprioceptive information from the hindlimb of the cat is now known to be relayed to the somatosensory thalamus and cortex via axons in the dorsolateral fasciculus and a medullary relay in nucleus z. The aim of this study was to identify nucleus z in the rat, to locate the cells of origin of spinal afferents to nucleus z, and to determine whether they are collaterals of the dorsal spinocerebellar tract. The location and extent of nucleus z were studied by filling the axon terminals of collaterals of the dorsal spinocerebellar tract (dsc) with horseradish peroxidase (HRP), which was injected into the inferior cerebellar peduncle. Nucleus z in the rat was found to be similar in location to nucleus z in other mammals. It was located just below the dorsal surface of the medulla, bounded laterally by the rostral pole of the cuneate nucleus and medially by the nucleus of the solitary tract. The cells of origin of the spinal afferents to nucleus z were studied by using the retrograde transport of HRP. They were located in Clarke's column (dorsal nucleus) and in lamina 10 of the dorsal horn. They were similar in location and morphology to neurons giving rise to the dorsal spinocerebellar tract, but were smaller in average diameter. A double retrograde labeling technique was used to determine whether the spinal afferents to nucleus z are collaterals of neurons giving rise to the dsc. It was estimated that up to 92% of the spinal afferents to nucleus z were collaterals of dsc neurons, while approximately 3% of all dsc neurons gave rise to collaterals terminating in nucleus z.     

Down syndrome and beta-amyloid deposition

PURPOSE OF REVIEW: Exciting new therapeutic approaches to the treatment or prevention of Alzheimer's disease involve preventing, slowing or reversing beta-amyloid accumulation. These interventions may also apply to the treatment of Alzheimer's disease in Down syndrome. The purpose of the current review is therefore to summarize developments and advances in our understanding of beta-amyloid pathogenesis in Down syndrome over the past year. RECENT FINDINGS: A shift in research to a focus on early events in beta-amyloid pathogenesis in Down syndrome has led to several novel observations. Several authors have reported the accumulation of both soluble and intracellular beta-amyloid before extracellular beta-amyloid (senile plaques) in Down syndrome. Increases in beta-amyloid levels in Down syndrome may reflect the increased expression and protein levels of beta-site amyloid precursor protein cleavage enzyme 2 on chromosome 21. The impact of the accumulation of beta-amyloid may have differential effects on development and aging in Down syndrome. SUMMARY: The past year has seen significant advances in our understanding of beta-amyloid pathogenesis and the functional consequences of beta-amyloid accumulation in Down syndrome. However, there are still large gaps in our knowledge of the pathways involved in beta-amyloid degradation and clearance. It will be critical to conduct clinical trials to test therapeutic strategies that may reduce beta-amyloid in Down syndrome directly to determine the optimal age and dose for specific interventions. Given the differences in the mechanism of beta-amyloid accumulation in Down syndrome, careful consideration needs to be given to potential clinical trials to treat this disorder.     

Altered expression of preproenkephalin and prodynorphin mRNA in a genetic model of paroxysmal dystonia

The dtsz mutant hamster represents a model of primary paroxysmal dystonia, in which dystonic episodes occur in response to stress. Previous examinations demonstrated striatal dysfunctions in dtsz hamsters. In the present study, in situ hybridization was used to examine preproenkephalin and prodynorphin expression as potential indices of imbalances between the striatopallidal and striatonigral pathways. Brain analyses were performed in dtsz hamsters under basal conditions, i.e., in the absence of dystonia, as well as mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In the striatum the basal expression of prodynorphin tended to be higher, while that of preproenkephalin tended to be lower in mutant hamsters in comparison to non-dystonic control hamsters. Significant basal changes were restricted to higher levels of prodynorphin in the ventrolateral striatum and lower prodynorphin and preproenkephalin mRNA expression in the hippocampus and/or in subregions of the hypothalamus. After stressful stimulation, the neuropeptides increased in several regions in both animals groups. In comparison to stimulated control hamsters, a significantly lower prodynorphin expression was found in several limbic areas of stimulated mutant hamsters during the manifestation of dystonia, while preproenkephalin mRNA was significantly lower in the anterior and dorsal striatal subregions and in nucleus accumbens. Since changes in the expression of these opioid peptides have been suggested to be related to abnormal dopaminergic activity, the present findings may reflect disturbances in striatal dopaminergic systems, and also in limbic structures in the dtsz mutant, particularly during the expression of dystonia.     

The effects of perinatal anoxia or hypoxia on hippocampal kindling development in rats

The effects of anoxia and hypoxia (3% oxygen) at 10–12 post days of age on the development of ventral hippocampal kindling and its transfer to the contralateral ventral hippocampus were studied in adult male Sprague-Dawley rats. During oxygen deprivation, the heart rate decreased to 15% of the prehypoxic value in the animals exposed to anoxia and 40% in those exposed to hypoxia. As is observed in asphyxia of human newborns, our study included both ischemia and hypoxia. The susceptibility to kindling, which was measured by kindling rate, afterdischarge threshold, generalized seizure threshold, and total afterdischarge duration to stage 5, had a tendency to be enhanced in rats exposed to hypoxia compared with controls. The facilitating effects on primary site kindling were enhanced in the animals exposed to hypoxia compared with those exposed to anoxia. Transfer, which was indicated by kindling rate and afterdischarge threshold, was also slightly facilitated in the rats exposed to anoxia or hypoxia in the perinatal period. These results reveal that perinatal oxygen deficiency may not be sufficient to lead to the development of temporal lobe epilepsy. However, it is possible that perinatal hypoxia results in some pathophysiological change in the brain which leads to greater seizure susceptibility in adulthood.     

Circulating angiotensin II activates neurones in circumventricular organs of the lamina terminalis that project to the bed nucleus of the stria terminalis

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo- and magnocellular divisions of the paraventricular nucleus. Fos-labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB-gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double-labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.     

Blood flow through cerebral collateral vessels one month after middle cerebral artery occlusion

Acute occlusion of a middle cerebral artery (MCA) reduces cerebral blood flow in normotensive Wistar-Kyoto rats (WKY) and in stroke-prone spontaneously hypertensive rats (SHRSP). The goal of this study was to determine whether MCA occlusion produces a sustained reduction in cerebral blood flow or whether collateral vessels restore blood flow to normal levels. We measured blood flow through cerebral collateral vessels to the territory of the occluded MCA and to homologous tissue of the other hemisphere in WKY 1 month after occlusion of the MCA. Cerebral blood flow, measured with microspheres, was restored to normal levels under control conditions in the territory of the occluded MCA. During vasodilatation produced by seizures, blood flow and vascular conductance were increased to similar levels in tissue distal to the site of MCA occlusion and in the homologous tissue of the other hemisphere. MCA occlusion did not produce infarction in any of the WKY. In contrast, 1 month after MCA occlusion in SHRSP, a large atrophic infarct was invariably present in the territory of the occluded MCA. The number of collateral vessels to the territory of the MCA do not differ in SHRSP and WKY. Internal diameter and orientation of the anastomotic vessels differ in SHRSP and WKY. We conclude that, after 1 month of MCA occlusion, changes in the collateral vessels supplying the territory of the occluded MCA in WKY were sufficient to restore blood flow to normal under control conditions and to virtually normal levels during vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic predisposition and the development of posttraumatic stress disorder in an animal model.

BACKGROUND: Exposure to extremely stressful events can lead to Posttraumatic stress disorder (PTSD). Due to the complexity of PTSD, animal models have been designed and advanced to address the role of psychosocial stressors in the etiology; however, the apparent role of genetics in susceptibility to PTSD-like behaviors in animals remains unexplored. METHODS: An animal model of congenital learned helpless (cLH) behavior has been used to study the effects of genetic disposition as a risk factor for the development of PTSD-like behaviors. Animals were monitored for changes in pain tolerance, spatial memory and hypothalamic-pituitary-adrenal functioning after re-exposure to intermittent stress in the presence and absence of situational cues. RESULTS: Exposure to stress resulted in an increase in pain tolerance in the cLH animals. In the spatial memory test 80% of the cLH animals manifested a decrease in performance after exposure to stress. These animals also had a blunted poststress corticosterone response. CONCLUSIONS: The genetic learned helpless animal model exhibited physiologic symptoms of analgesia, cognitive deficits and hyporesponsivity of the hypothalamic-pituitary-adrenal axis similar to those observed in human subjects with PTSD. It is proposed that the cLH model may be a valuable tool for exploring the role of genetic predisposition in the etiology of PTSD.