An examination of the synergistic interaction of ethanol and thiamine deficiency in the development of neurological signs and long-term cognitive and memory impairments.

BACKGROUND: The prolonged and heavy consumption of ethanol has been associated with thiamine deficiency and a wide range of cognitive and memory impairments. The present study was undertaken to test the hypothesis that ethanol and thiamine deficiency act synergistically, producing more severe clinical neurological disturbances and cognitive and memory impairments than either thiamine deficiency or chronic ethanol alone. METHODS: The acute neurological and long-term behavioral consequences of combined chronic (32 weeks) ethanol consumption (20% v/v in drinking water) and three separate 4-week long episodes of dietary thiamine deficiency (ET/TD) versus ethanol (ET) or thiamine deficiency (TD) treatments alone were examined in male Sprague Dawley rats aged 12 weeks at the start of treatment. RESULTS: The ET/TD group lost less weight than the TD group during each episode of thiamine deficiency. Contrary to expectations, the progression and severity of ataxia, impaired righting reflexes, and opisthotonic posturing were similar in the ET/TD and TD groups. None of the ET animals displayed any neurological or behavioral symptoms during treatment. After withdrawal from ethanol and a 7-week recovery period, none of the groups differed in spontaneous activity. On subsequent testing, the ET group displayed a significant increase in perseverative responding in a spontaneous alternation task. A small but significant proportion of ET/TD (23%), ET (17%), and TD (8%) animals were unable to reach criterion on an initial nonmatching-to-position task (NMTP) or in two subsequent reversals of the matching and NMTP tasks, which indicated persistent learning impairments. A large proportion of animals in each of the three groups demonstrated significantly reduced accuracy compared with controls at longer delays of matching-to-position tasks (MTP), but only the ET group was consistently impaired at the shorter delays. There were no significant correlations between blood ethanol concentration and any of the learning and memory measures. CONCLUSIONS: These results indicate that the interaction of chronic ethanol consumption and bouts of TD is both domain specific and not always synergistic. Learning and reference memory appear to be sensitive to a synergistic interaction of ET and TD, whereas short-term working memory disturbances are most affected by ET and neurological symptoms are most associated with TD. Furthermore, neither the presence of neurological symptoms nor blood ethanol concentrations appear to be good predictors of learning and memory deficits.

Attentional dysfunction associated with posttraumatic stress disorder among rape survivors.

Posttraumatic stress disorder (PTSD) is characterized by subjective reports of decreased concentration and an inability to sustain attention. Some empirical validation of these symptoms has been demonstrated via reduced performance on attentional tests among war veterans with PTSD. However, the significance of such findings is unclear given high co-morbidity with other psychiatric, neurologic, and substance abuse disorders among veterans. The present study examined neuropsychological functioning among rape survivors with PTSD, a patient population with comparatively low rates of psychiatric co-morbidity. Rape survivors with PTSD (PTSD+; n = 15) were compared to rape survivors without PTSD (PTSD-; n = 16) and age- and education-matched nontraumatized controls (CTRL; n = 16) on tests of attention. Performance of the PTSD+ group was significantly worse than the other groups on measures of sustained and divided attention, but not on shifting of visuospatial selective attention. Performance differences were not attributable to co-morbid psychiatric disorders or substance abuse. The implications of these findings regarding the effects of trauma on attentional functions are discussed.

Increased histamine release and granulocytes within the thalamus of a rat model of Wernicke's encephalopathy.

The current study examined the possible role of increased histamine release and granulocyte activity in the vascular changes that precede the onset of necrotic lesions with the thalamus of the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke's encephalopathy (WE). An increase in histamine release and the number of granulocytes was observed in lateral thalamus on day 9 and in medial thalamus on day 10 of PTD treatment, a duration of thiamine deficiency associated with perivascular edema in this brain region. Within the hippocampus, histamine release was significantly increased on day 9, declined to control levels on days 10-12, and was significantly elevated on days 12-14. No granulocytes were observed in hippocampus of either PTD or control rats. These observations suggest that the release of histamine from nerve terminals and histamine and other vasoactive substances from granulocytes may be responsible for thiamine deficiency-induced vascular breakdown and perivascular edema within thalamus.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy.

A large increase in the number and percentage of degranulating mast cells was observed within thalamus of rats after 6-7 days of thiamine deficiency (TD). No mast cells were detected in the inferior olivary and lateral vestibular nuclei, which are also severely damaged by TD. After 11-12 days of TD, the number of ED2 immunopositive macrophages increased in thalamus. In the brainstem nuclei, an increase in the number of macrophages occurred much earlier in treatment (i.e. day 6). An increase in GFAP-positive astrocytes within thalamus occurred after the changes in mast cells and prior to the increase in macrophages. In brainstem, reactive astrocytes appeared along with the increase in macrophages. These data suggest that mast cell degranulation is a very early response induced by TD, and the resultant release of cytokines and other chemical mediators may play critical roles in both the early vascular damage and eventual tissue destruction within thalamus, but not within brainstem. These results also suggest that macrophages and reactive astrocytes may play more direct roles in the pathogenesis of brainstem lesions.

Thiamine deficiency-induced disruptions in the diurnal rhythm and regulation of body temperature in the rat.

In the present study, diurnal rhythm and regulation of body temperature were monitored during and several weeks following pyrithiamine-induced thiamine deficiency (PTD group, n=8) or pairfeeding (control group, n=9). A significant decline of core body temperature and a disruption of its diurnal rhythm were observed at varying stages of PTD treatment. Following thiamine administration and return to thiamine-fortified chow, body temperature continued to fall and several days transpired before body temperature and its diurnal rhythm were returned to normal. When exposed to warm and cold environments, no significant group differences were observed in either the maximum temperature change or the time elapsed to reach maximal temperature change. Histological examination revealed necrotic lesions in thalamus and mammillary body in the PTD group characteristic of Wernicke's encephalopathy. No significant damage was observed in the medial preoptic and suprachiasmatic nuclei, brain regions involved in the regulation of body temperature and circadian rhythm. These findings suggest that hypothermia and disruption of the diurnal rhythm of body temperature can be reversed by restoration of adequate thiamine levels and are related to biochemical and physiological disturbances rather than gross structural changes.

Learning and memory in rape victims with posttraumatic stress disorder.

OBJECTIVE: Studies have shown memory deficits among combat veterans with posttraumatic stress disorder (PTSD); however, high rates of comorbid conditions, including alcoholism, make it difficult to definitively associate these findings with the PTSD diagnosis. In this study the authors examined memory functioning among rape survivors without alcoholism or substance abuse but with PTSD. METHOD: Rape victims with (N = 15) and without (N = 16) PTSD were compared to age- and education-matched nontraumatized comparison subjects (N = 16) on measures of learning and memory. RESULTS: The subjects with PTSD performed significantly worse than the other groups on delayed free recall. The deficits were ameliorated by cueing and recognition testing. CONCLUSIONS: Recall deficits in noncombat PTSD patients strengthen the theory that memory deficits are associated with the PTSD diagnosis. The deficits were mild and were not attributable to comorbid depression, anxiety, or substance abuse.

Effects of lesions of thalamic intralaminar and midline nuclei and internal medullary lamina on spatial memory and object discrimination.

Male Sprague-Dawley rats received either radiofrequency lesions of the lateral internal medullary lamina (IML) or ibotenic acid lesions of the lateral intralaminar nuclei (ILN) and midline nuclei (MLN) or sham treatment. Neither lesion group was impaired in the retention of 3 object pair discriminations acquired before surgery nor in the acquisition of a new object pair after surgery. Rats with ILN, but not IML, lesions were impaired in acquiring an initial and 5 subsequent hidden platform locations in a water maze task. These results suggest that damage to both ILN and MLN are needed to produce spatial learning deficits and that extensive damage to the IML or ILN has no detectable effects on retrograde or anterograde memory of object discriminations.

Increased cerebral free radical production during thiamine deficiency.

Concentration of reactive oxygen species (ROS) and the antioxidant glutathione (GSH) was measured in thalamus and cortex after 13 and 14 days of pyrithiamine-induced thiamine deficiency (PTD) in the rat. The concentration of ROS was significantly elevated in thalamus and cortex on day 14 when righting reflexes were absent and spontaneous seizures occurred. No significant changes in GSH concentration were observed in thalamus or cortex on either day of treatment. These findings suggest that increased formation of free radicals occurs during the more acute symptomatic stage of thiamine deficiency and may contribute to the structural damage described in this model of Wernicke's encephalopathy.

Cortical and subcortical white matter damage without Wernicke's encephalopathy after recovery from thiamine deficiency in the rat.

The relative etiologic roles of ethanol and thiamine deficiency in the cortical atrophy and loss of cerebral white matter in chronic alcoholics are uncertain. The present study examined the distribution of degenerating axons within cortical and subcortical tracts 1 week after recovery from early to late symptomatic stages of thiamine deficiency in the absence of ethanol in Sprague-Dawley rats. The brains of rats exposed to an early symptomatic stage of pyrithiamine-induced thiamine deficiency, 12-13 days of treatment, contained degenerating axons in corpus callosum, anterior commissure, external and internal capsules, optic and olfactory tracts, and fornix and mammillothalamic tracts. A dense pattern of degenerating axons was evident in layers III-IV of frontal and parietal cortex. Less intense and more evenly distributed degenerating axons were present in layers IV-VI of frontal, parietal, cingulate, temporal, retrosplenial, occipital, and granular insular cortex. Neuronal counts in mammillary body nuclei and areal measurements of the mammillary body were unchanged from controls and the thalamus was relatively undamaged. In animals reversed at later and more advanced symptomatic stages of thiamine deficiency, 14-15 days of treatment, degenerating axons were found in other cortical regions and hippocampus and there was extensive neuronal loss and gliosis within mammillary body and medial thalamus. These results demonstrate that a single episode of thiamine deficiency can selectively damage cortical white matter tracts while sparing the thalamus and mammillary body and may be a critical factor responsible for the pathological and behavioral changes observed in alcoholics without Wernicke's encephalopathy.

The effects of lesions to thalamic lateral internal medullary lamina and posterior nuclei on learning, memory and habituation in the rat.

The behavioral effects of radiofrequency lesions to the lateral internal medullary lamina region (IML) or the posterior region (Po: containing the parafascicular and posterior nuclei) of the thalamus were compared to sham operated controls. Subjects were pre-operatively trained and then tested for post-operative retention of a NMTP task. Whereas the Po-lesion group was impaired only on long delays (60, 90 s), the IML-lesion group was impaired on retention and re-acquisition and demonstrated lower performance at all delays (5-90 s) of the NMTP task. Post-operative training and testing was conducted on three additional tasks: Morris water maze, acoustic startle, and passive avoidance. The IML-lesion group was impaired in finding a hidden and visual platform in the Morris water maze, demonstrated a blunted response but normal habituation to an acoustic startle stimulus, and showed normal retention of a passive avoidance task. On those three tasks, the performance of the Po-lesion group was similar to controls. In the IML-lesion group, neuronal loss resulting from axotomy and/or transneuronal degeneration was observed within nuclei of the midline and anterior thalamus and the mammillary body. These results suggest that lesions to the IML region disrupt a range of cognitive functions and produce pathological destruction in distant brain regions; whereas damage to the posterior thalamus causes spatial delay-sensitive deficits.

Neuropathology of thiamine deficiency: an update on the comparative analysis of human disorders and experimental models.

This paper provides a re-examination of the neuroanatomical consequences of thiamine deficiency in light of more recent studies of human disorders and models of experimental thiamine deficiency. A major goal is to elucidate the relative roles of thiamine deficiency and chronic alcohol consumption in the pathogenesis of Wernicke-Korsakoff syndrome (WKS). Particular emphasis is placed on the role of thiamine deficiency in lesions to basal forebrain, raphe, locus coeruleus, white matter and cortex and their role in the cognitive and memory disturbances of human WKS and experimental models of thiamine deficiency.

Thiamine deficiency in rats produces cognitive and memory deficits on spatial tasks that correlate with tissue loss in diencephalon, cortex and white matter.

Exploratory activity, spontaneous alternation, learning and memory abilities were examined in the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke-Korsakoff's syndrome and pair-fed controls (CT). PTD and CT animals showed normal retention of a single trial of a passive avoidance task acquired prior to the acute stages of thiamine deficiency. While there were no significant group differences in spontaneous activity, PTD animals with extensive damage to internal medullary lamina (IML-lesioned) of thalamus and mammillary body nuclei demonstrated a significant decrease in spontaneous alternation and were significantly impaired in learning both the initial spatial non-matching-to-position (NMTP) task and the reverse MTP task. PTD animals without IML damage (IML-spared) were only impaired on the acquisition of NMTP. Examination of response patterns suggest that the learning impairment was related to an inability to adopt or shift to the appropriate response rule. Performance of PTD IML-lesioned animals on NMTP mixed-delay sessions (4, 30, 60, 90 s) was similar to controls and PTD IML-spared, but was significantly lower on MTP delay trials. These IML-lesioned rats also had significant reductions in thickness of frontal and parietal cortex, corpus callosum and severe neuronal loss in anterior and reticular thalamic nucleic. Four PTD IML-lesioned animals that were unable to learn the NMTP task had more extensive cortical, white matter and thalamic damage than the PTD IML-lesioned animals that did learn the task. These results demonstrate that thiamine deficiency in the rat produces behavioral changes ranging from mild cognitive deficits to severe learning and memory impairments. Pathologic damage following a bout of thiamine deficiency also varies from neuronal loss in select thalamic nuclei to tissue loss in large regions of thalamus, mammillary bodies and cortex. Learning and memory deficits are closely related to the degree of cortical and diencephalic damage.

Excitotoxic cytopathology, progression, and reversibility of thiamine deficiency-induced diencephalic lesions.

The present study examined the cytopathological changes within diencephalon of a rat model of Wernicke's encephalopathy and determined whether administration of thiamine at various intervals after onset of neurological signs can arrest or reverse the cytopathological process. Electron microscopic examination of the brains from animals sacrificed at four progressively severe stages of pyrithiamine-induced thiamine deficiency (PTD) revealed neurocytopathological changes identical to those that have been described in glutamate-induced excitotoxic lesions. These degenerative changes occurred in gelatinosus (Ge) and anteroventral ventrolateral (AVVL) nuclei at an early symptomatic stage and in the ventroposterolateral (VPL), ventroposteromedial (VPM), and ventrolateral (VL) nuclei at slightly later stages of PTD. Light microscopic evaluation of separate groups of PTD rats administered thiamine at each of the same four neurologic stages and allowed to recover for 1 week demonstrated that thiamine treatment is more effective when administered at earlier stages. However, Ge, AVVL, and VPL nuclei sustain severe damage even when thiamine is administered prior to acute neurologic signs. Furthermore, pathologic changes in the mammillary and several midline intralaminar nuclei begin after thiamine administration and reinstitution of thiamine-replete diet to animals in more severe stages of thiamine deficiency. These and other recent findings suggest that excitotoxic and possibly apoptotic mechanisms may mediate neuronal degeneration in the PTD rat model of Wernicke's encephalopathy, and that multiple factors conducive to excitotoxicity may act in concert to produce this syndrome.

Pathogenesis of diencephalic lesions in an experimental model of Wernicke's encephalopathy.

The relationship of thiamine deficiency to Wernicke's encephalopathy has been well established. The biochemical bases and physiologic mechanisms responsible for the pathologic changes and their selective distribution within the brain remain controversial. The present paper reviews recent biochemical, histopathological and pharmacological evidence of a glutamate-mediated excitotoxic mechanism of neuronal loss in pyrithiamine-induced thiamine deficiency (PTD), a rat model of Wernicke's encephalopathy. A mechanistic model involving the unique combination of thiamine deficiency-induced impairment of energy metabolism, increased release of histamine, and multidirectional glutamate inputs is presented to explain the selective vulnerability of thalamic nuclei to excitotoxic lesions in the PTD model.

Histamine-mediated neuronal death in a rat model of Wernicke's encephalopathy.

Three experiments were conducted to examine the role of histamine in neuronal degeneration in a rat model of Wernicke's encephalopathy induced by an acute bout of pyrithiamine-induced thiamine deficiency (PTD). In the first experiment, histamine levels in medial thalamus of freely moving PTD rats measured by microdialysis were increased (180% of controls) at a prelesion stage of thiamine deficiency (treatment day 12) and further elevated 48 hr later (380%) in the same animals when necrosis was evident. Histamine levels in dialysates of the hippocampus collected simultaneously from the same animals were unchanged at either stage of thiamine deficiency. Glutamate levels in microdialysates from the same animals were unchanged at the prelesion stage but were significantly elevated on the second collection day. In a second experiment, separate groups of PTD and pairfed control (CT) rats were infused continuously with either alpha-fluoromethylhistidine (FMH; 80 mg/day, i.p.), an irreversible inhibitor of histamine synthesis, or saline. FMH pretreatment produced a significant protection against PTD-induced neuronal loss within the midline-intralaminar and anteromedial thalamic nuclei, but had no effect on damage to ventrolateral nuclei, anteroventral nucleus, or the mammillary bodies. In a third study, histamine (80 micrograms, free base) or vehicle was directly infused into the same region of medial thalamus dialyzed in experiment 1. Histamine infusion into prelesion PTD but not CT animals resulted in severe neuronal loss and gliosis. Infusion of vehicle into the same regions of PTD and CT rats produced a mild gliosis restricted to the needle tract with no evidence of neuronal loss. These observations together with recent evidence of a histamine enhancement of glutamate receptor activation suggest that early histamine release may contribute significantly to glutamate-N-methyl-D-aspartate (NMDA)-mediated excitotoxic neuronal death in thiamine deficiency-induced Wernicke's encephalopathy.

Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.

We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.

Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.

1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/- 1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.

A single intramesencephalic injection of brain-derived neurotrophic factor induces persistent rotational asymmetry in rats.

Brain-derived neurotrophic factor (BDNF) is expressed in dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the ventral tegmental area and provides trophic support for these neurons in vitro. To study the effects of BDNF on the nigrostrital dopaminergic system in vivo, we administered a single, unilateral injection of BDNF into the medial SNpc of rats and evaluated rotational behavior, striatal levels of dopamine and metabolites, and number of dopaminergic neurons in the SNpc. We found that a single injection of 2 or 3 micrograms of BDNF, but not of vehicle, caused a persistent increase in the net number of amphetamine-induced rotations/min contraversive to the site of injection. The pattern of rotation is consistent with increased activity of the nigrostriatal dopaminergic system on the side of injection. The amphetamine-induced contraversive rotation could be blocked by administration of the dopaminergic antagonist haloperidol. Apomorphine, a direct-acting dopaminergic agonist, did not induce rotation. Levels of dopamine in the striatum and number of dopaminergic neurons in the SNpc were similar in BDNF- and vehicle-treated animals. The increase in contraversive rotations persisted for up to 12 months after a single injection of BDNF.

Extracellular glutamate is increased in thalamus during thiamine deficiency-induced lesions and is blocked by MK-801.

The current study measured extracellular fluid (ECF) levels of excitatory amino acids before and during the onset of thiamine deficiency-induced pathologic lesions. Male Sprague-Dawley rats were treated with daily pyrithiamine (0.25 mg/kg i.p.) and a thiamine-deficient diet (PTD). Microdialysates were simultaneously collected from probes inserted acutely via guide cannulae into right paracentral and ventrolateral nuclei of thalamus and left hippocampus of PTD and pair-fed controls. Hourly samples were collected from unanesthetized and freely moving animals. Basal levels obtained at a prelesion stage (day 12 of PTD treatment) were unchanged from levels in pair-fed controls. In samples collected 4-5 h after onset of seizures (day 14 of PTD), the levels of glutamate were elevated an average 640% of basal levels in medial thalamus and 200% in hippocampus. Glutamine levels declined, taurine and glycine were elevated, and aspartate, GABA, and alanine were unchanged during this period. Within 7 h after seizure onset glutamine was undetectable in both areas, whereas glutamate had declined to approximately 200% in thalamus and 70% in hippocampus. No significant change in glutamate, aspartate, or other amino acids was observed in dialysates collected from probes located in undamaged dorsal-lateral regions of thalamus. Number of neurons within ventrolateral nucleus of thalamus was significantly greater in PTD animals in which the probe was dialyzed compared with nondialyzed, suggesting that removal of excitatory amino acids was protective. No significant pathologic damage was evident in hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of NBm lesions on T-maze performance and thalamic biochemistry.

Fisher 344 rats underwent bilateral nucleus basalis magnocellularis (NBm) lesioning followed by testing in a delayed nonmatching-to-sample T-maze task. Both lesion and control animals acquired the task although the NBm animals were mildly impaired on acquisition and on trials to criterion. Increasing the delay reduced accuracy of performance equally in both groups. The NBm lesion did not alter the level of several thalamic amino acids. These data indicate that NBm lesioning does not produce a significant impairment in working or reference memory in this task and supports the hypothesis that NBm lesioning impairs attention.