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P Boksa

Publications and source records attributed to P Boksa.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hippocampal and hypothalamic type I corticosteroid receptor affinities are reduced in adult rats born by a caesarean procedure with or without an added period of anoxia.

Brief periods of hypoxia during labour and birth are a frequent occurrence. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia in both adult and immature animals. The hippocampus also contains the highest concentration of corticosteroid receptors of any brain region and both mineralocorticoid (type I) receptors and glucocorticoid (type II) receptors in the hippocampus play a role in the regulation of basal diurnal and stress-induced glucocorticoid secretion. Given this background, the aim of this study was to test whether an acute period of anoxia during the birth process may have lasting effects on CNS corticosteroid receptor levels and/or pituitary-adrenocortical function. Type I and type II corticosteroid receptor binding sites in the hippocampus and hypothalamus were compared in adult rats that had been born vaginally, born by a Caesarean procedure or born by a Caesarean procedure with 5, 10 or 15 min of added anoxia. Using 14 nM [3H]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50% in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vaginally born controls. Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [3H]corticosterone, with no change in numbers of receptors. Birth condition had no effect on glucocorticoid receptor binding capacities in the hippocampus or hypothalamus. A small increase in basal corticosterone secretion during the diurnal trough was observed in adult animals that had been born by Caesarean section with 5 or 15 min of added anoxia. The plasma corticosterone response to a 20-min restraint stress was reduced in adult animals born by Caesarean section with or without an added period of anoxia, in comparison to vaginally born controls. However the adrenocorticotropin response to stress was largely unaffected by birth condition. The results indicate that an acute birth insult is sufficient to produce long-lasting alterations in hippocampal and hypothalamic mineralocorticoid receptor sites, accompanied by changes in basal and stress-induced glucocorticoid secretion.

Adrenocorticotropic Hormone↗
PubMed1995

Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury.

Injured neurons in the CNS are known to synthesize high levels of proliferation related oncogene products and heat shock proteins without dividing. Statin is a cell cycle regulated nuclear phosphoprotein, selectively associated with the non-proliferative state in a wide variety of cell types. In the present study, neuronal statin was examined following lethal or sublethal neuronal injuries in the hippocampus of Alzheimer's disease patients, in rats receiving kainate lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's disease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss. Entorhinal cortex lesioned rats showed a transient induction of statin between 2 and 6 days post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicating that increased statin levels are not secondary to neuronal degeneration and are not necessarily accompanied by irreversible neuronal death. It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.

Alzheimer Disease↗
PubMed1995

Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning.

Basal and stress-induced pituitary-adrenocortical (PA) and sympathetic adrenomedullary (SAM) function was investigated in rats exposed to chronic intermittent cold stress (4 degrees C for 4 h a day for 21 days; CHR). We found that basal plasma levels of corticosterone (B), corticosteroid-binding-globulin, ACTH, epinephrine (E) and norepinephrine (NE) were similar in CHR and control (CTL) animals. In contrast, activity of the adrenal catecholamine-synthesizing enzyme tyrosine hydroxylase, but not phenylethanolamine-N-methyl transferase, was significantly elevated in CHR compared to CTL. Following exposure to a heterotypic stressor (20 min restraint), plasma levels of B were significantly higher in CHR than CTL, but the stress-induced levels of E and NE were not different between groups. These data suggest that, although basal PA function is not altered by exposure to chronic intermittent cold stress, components of the SAM system are affected by this paradigm, and that co-ordinate facilitation of both PA and SAM responses to a novel stressor is not a necessary consequence of exposure to chronic intermittent stress.

Adrenal Medulla↗
PubMed1995

Effects of a period of asphyxia during birth on spatial learning in the rat.

The present study aimed to test whether an acute period of asphyxia during birth in the rat results in long-term alterations in CNS function. Morphologic studies have indicated that the hippocampus is particularly vulnerable to perinatal anoxia. Thus, the present study tested adult rats, which had undergone acute birth asphyxia, for their performance in spatial learning and memory tasks associated with the hippocampus. Rat fetuses on the day of birth were submitted to an acute period of complete asphyxia by submersion of the isolated uterus into a water bath for 5-20 min before delivery of the pups. Control animals were either born vaginally or delivered by rapid cesarean section. At 1.5 mo of age, rats that had undergone 15 min of birth asphyxia showed no deficit in acquisition of spatial learning, measured as latency to find a hidden platform in the Morris water maze. However, at 4 mo of age, separate groups of rats, which had undergone 10, 15, or 20 min of birth asphyxia, showed a deficit in initial acquisition of the spatial learning task compared with vaginally born controls, whereas the 5-min group performed similarly to controls. After overtraining, there was no difference among groups on short-term (1 wk) retention of the spatial navigation task; however, asphytic animals tested at 1.5 mo and retested at 4 mo showed a slight deficit in retention on retest. Animals that had undergone 15 min of birth asphyxia weighed less than did vaginally born animals, but showed no deficit in swimming ability, spontaneous alternation in a T maze, or other sensorimotor indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

GABAA receptor-mediated inhibition of N-methyl-D-aspartate-evoked [3H]dopamine release from mesencephalic cell cultures.

Direct activations of both GABAA and GABAB receptors are known to hyperpolarize dopaminergic neurons. However systemic or intra-ventral tegmental administration of a GABAA receptor agonist produces paradoxical depolarization of mesencephalic dopaminergic neurons and increases dopamine release. Thus indirect excitation appears to preclude observation of inhibitory GABAA effects on dopamine release in intact tissue. The present study used cultures of isolated cells from rat ventral mesencephalon to characterize effects of GABAA and GABAB receptor activation on evoked dopamine release. The GABAA receptor agonist, muscimol, produced a potent and complete inhibition of N-methyl-D-aspartate (NMDA)-evoked [3H]dopamine release. This effect was blocked by the GABAA receptor antagonist, picrotoxin, and enhanced by flunitrazepam. Omission of Mg2+ greatly reduced the inhibitory effect of muscimol on NMDA-evoked [3H]dopamine release. Muscimol had little or no effect on [3H]dopamine release evoked by the non-NMDA receptor agonists, quisqualate and kainate. The GABAB receptor agonist, baclofen, slightly inhibited NMDA-evoked [3H]dopamine release and had no effect on release evoked by quisqualate or kainate. Endogenous GABA released by the mesencephalic cells also appeared to inhibit NMDA-evoked [3H]dopamine release mainly via a GABAA receptor-mediated mechanism. This is suggested by the observations that NMDA-evoked [3H]dopamine release was potentiated by picrotoxin but not by the GABAB receptor antagonist, phaclofen, and that blockade of extracellular GABA removal, with amino-oxyacetic acid and beta-alanine, inhibited NMDA-evoked [3H]dopamine release in a picrotoxin-sensitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Statin, a marker of cell cycle arrest, is overexpressed during the early phase of delayed NMDA toxicity in hippocampal cell cultures.

Statin is a 57-kDa protein exclusively expressed in nuclei of nonproliferating mammalian cells. Recent studies have suggested that statin may play a role in the maintenance of growth arrest. Several lines of evidence also support the notion that a variety of genes and gene products are modulated during cell proliferation and cell death. The present study examined the possibility that statin expression could be modulated during neuronal injury using N-methyl-Daspartate (NMDA)-induced toxicity to rat embryonic hippocampal cultures as a model. Immunocytochemical studies using a monoclonal antibody to statin revealed a prominent nuclear localization of statin in cultured hippocampal cells. Western blot analysis showed that this antibody recognizes a 57-kDa protein band, indicative of the presence of statin in this preparation. Brief exposure of hippocampal neurons to NMDA (500 microM) produced severe neuronal degeneration over the subsequent hours. NMDA-treated neurons markedly overexpressed statin. Both NMDA-induced neuronal toxicity and statin overexpression were prevented by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohept-5,10-imine hydrogen maleate (MK-801). Interestingly, time course studies indicate that the increased expression of statin observed following NMDA exposure clearly preceded the appearance of the first signs of neuronal death as determined by vital staining. In addition, exposure of hippocampal neurons to the Ca2+ ionophore, A23187, produced a marked increase in statin immunodetection, indicating that statin expression is likely regulated in a Ca(2+)-dependent manner. Thus, these results show that statin, which is expressed at low levels in embryonic rat cultured hippocampal neurons, is rapidly overexpressed following a toxic insult produced by the activation of the NMDA receptor. The observation that statin overexpression occurs prior to neuronal death raises the possibility that the up-regulation of statin could be used as an early index of neuronal injury.

Animals↗
PubMed1994

The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion.

1. A single administration of the ganglion blocker, chlorisondamine (10 mg kg-1, s.c.) is known to produce a quasi-irreversible blockade of the central actions of nicotine in the rat. The mechanism of this persistent action is not known. It is also unclear whether chlorisondamine can block neuronal responses to excitatory amino acids and whether chronic blockade of nicotinic responses also occurs in the periphery. 2. Acute administration of chlorisondamine (10 mg kg-1, s.c.) to rats resulted in a blockade of central nicotinic effects (ataxia and prostration) when tested 1 to 14 days later, but caused no detectable cell death in tissue sections sampled throughout the rostrocaudal extent of the brain which were stained in order to reveal neuronal degeneration. 3. Long-term blockade of central nicotinic effects by chlorisondamine was not associated with significant alterations in the density (Bmax) of high-affinity [3H]-nicotine binding to forebrain cryostat-cut sections. 4. In cultured dissociated mesencephalic cells of the foetal rat, chlorisondamine and mecamylamine inhibited [3H]-dopamine release evoked by N-methyl-D-aspartate (NMDA, 10(-4) M), but only at high concentrations (IC50 approx. 600 and 70 microM, respectively). A high concentration of chlorisondamine (10(-3) M) had no effect on responses to quisqualate (10(-5) M) and only slightly reduced responses to kainate (10(-4) M). Mecamylamine (10(-3) M) was ineffective against both agonists. 5. In adult rat hippocampal slices, chlorisondamine depressed NMDA receptor-mediated synaptically-evoked field potentials, but again only at high concentrations (10(-4)-10(-3) M). Synaptic responses that were mediated by non-NMDA excitatory amino acid receptors were less affected. 6. In rat isolated superior cervical ganglion, electrically-evoked synaptic transmission was reduced 1 h after acute in vivo administration of chlorisondamine (0.1 mg kg-1, s.c.). However, in vivo administration of a higher dose (10 mg kg-1, s.c.) did not significantly affect ganglionic transmission when tested two weeks later, despite the continued presence of central nicotinic blockade.7. These results indicate that the persistent CNS nicotinic blockade by chlorisondamine is not accompanied by changes in nicotinic [3H]-nicotine binding site density or by neuronal degeneration in the brain; that at doses sufficient to produce nicotinic receptor blockade, chlorisondamine acts in a pharmacologically selective manner; and that chronic central blockade is not accompanied by long-term peripheral ganglionic blockade.

Amino Acids↗
PubMed1994

Regulation of the adrenomedullary catecholaminergic system after mild, acute stress.

The time course of regulation of rat adrenomedullary phenylethanolamine N-methyltransferase (PNMT) and tyrosine hydroxylase (TH) activity was studied after a single episode of 20-min restraint stress. Significant increases in PNMT and TH activity were observed 18 h after the beginning of the stress. The time course of acute stress-induced regulation of PNMT and TH was examined for the influence of neural and hormonal input. Unilateral denervation was performed, and the animals were exposed to a single episode of restraint. PNMT activity increased similarly in both the innervated and denervated adrenals, with a significant increase observed at 36 h after the stress. TH activity was similar in both denervated and innervated adrenals, with a significant increase observed at 24 and 36 h after stress. Finally, suppression of endogenous corticosterone with dexamethasone delayed the stress-induced increase in activity of PNMT but not TH. The present study indicates that increases in catecholamine biosynthetic enzymes can be observed after a single episode of mild, acute stress. In addition, glucocorticoids appear to be important in the time course of the stress-induced increase in PNMT but not TH activity, whereas neural input does not seem to affect the time course of these increases.

Acute Disease↗
PubMed1993

Brief cortisol exposure elevates adrenal phenylethanolamine N-methyltransferase after a necessary lag period.

The present study, using bovine adrenal medullary cells, characterized in detail the time course of regulation of phenylethanolamine N-methyltransferase activity following brief glucocorticoid exposure. Cortisol pulses (10(-4) and 10(-5) M), as short as 15 min, increased phenylethanolamine N-methyltransferase activity measured 2 days following cortisol exposure, with a required lag period of 18 h or more. Phenylethanolamine N-methyltransferase activity was increased 2 days following brief (2 h) exposure to cortisol in concentrations that reach the medulla in vivo (10(-6) to 10(-4) M). Phenylethanolamine N-methyltransferase activity following both continuous and 2 h pulses of 10(-5) M cortisol were reduced by the glucocorticoid receptor antagonist, RU 38486. A 2 h pulse of nicotine (10(-5) M) increased phenylethanolamine N-methyltransferase activity with a lag period of at least 18 h, while combination treatment of nicotine and cortisol (10(-4) M) produced significantly higher increases in phenylethanolamine N-methyltransferase compared to either treatment alone. Therefore, this study provides novel in vitro evidence for the regulation of adrenomedullary phenylethanolamine N-methyltransferase activity, following a necessary lag period, by acute changes in both cortisol and nicotine.

Adrenal Medulla↗
PubMed1993

Brain calcium channel related dihydropyridine and phenylalkylamine binding sites in Alzheimer's, Parkinson's and Huntington's diseases.

Disruptions of normal calcium (Ca2+) homeostasis in human aging processes, are well documented. The existence of at least four distinct types of Ca2+ channels, L-, T-, P-, and N-, have been reported in the central nervous system. Binding sites for clinically useful dihydropyridines (DHP) and phenylalkylamines (PA) are located on the L-type Ca2+ channels. In the present study, DHP/[3H]PN200-110 and PA/[3H](-)-D-888 binding parameters were determined in various brain areas obtained at autopsy from Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) disease patients, and healthy age-matched controls as a means to assess the integrity of L-type channels in these neurological disorders often associated with the aging brain. DHP and PA receptor binding parameters (KD and Bmax) were not significantly altered in any of the brain regions studied in AD and PD. However, a significant decrease in the maximal binding capacity of [3H]PN200-110 was observed in the striatum of HD patients. Taken together, this suggests that DHP and PA binding sites associated to L-type Ca2+ channels are mostly preserved in AD and PD brains. Accordingly, the use of DHP- and/or PA-related drugs in these neurological disorders should not be hindered by deficits in their related Ca2+ channel binding proteins.

Aged↗
PubMed1993

Muscarinic potentiation of excitatory amino acid-evoked dopamine release in mesencephalic cells: specificity for the NMDA response and role of intracellular messengers.

Of the five cloned muscarinic receptor subtypes, dopamine (DA) neurons in the substantia nigra and ventral tegmental areas have been shown to be selectively enriched with the mRNA for the m5 subtype, suggesting that muscarinic modulation of DA neurons may have a distinct pharmacology. In the present study we have used dissociated cell cultures of fetal rat ventral mesencephalon to characterize muscarinic modulation of DA neurons. [3H]DA release stimulated by activation of N-methyl-D-aspartate (NMDA) receptors was potentiated by carbachol, a mixed muscarinic-nicotinic agonist, and by oxotremorine-M, a muscarinic agonist. Neither carbachol nor oxotremorine-M had an effect on [3H]DA release evoked by the non-NMDA agonists, kainate or quisqualate. A nicotinic agonist, DMPP, had no effect on NMDA-stimulated release. Potentiation of NMDA-stimulated [3H]DA release by oxotremorine-M was inhibited by the broad spectrum muscarinic antagonist, QNB, and by low concentrations of a putative M1 antagonist, pirenzepine, while much higher concentrations of a purported M2 antagonist, AF-DX 384, were required to reverse the oxotremorine-M effect. The muscarinic antagonist, 4-DAMP, was active in a concentration range between that required for pirenzepine and AF-DX 384. Further experiments examined intracellular messenger mechanisms coupled to the muscarinic receptors modulating NMDA-stimulated [3H]DA release. In contrast to oxotremorine-M, two muscarinic agents with only weak partial agonism with respect to phosphoinositide turnover, pilocarpine and arecoline, had no effect on NMDA-stimulated [3H]DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1993

Glucocorticoid receptors in bovine adrenal medullary cells in culture: regulation by cyclic nucleotides.

Glucocorticoid receptor levels within a given cell determine the glucocorticoid effect in the target tissue. Glucocorticoid receptors are present in adrenal medullary cells in culture where they are involved in the regulation of catecholamine biosynthesis. Modulation of glucocorticoid receptor protein and/or messenger RNA levels in response to cyclic nucleotides has been found in various cell types. In this study, we have investigated the effects of cyclic AMP and cyclic GMP on glucocorticoid receptor binding and glucocorticoid receptor-mediated function in Percoll-isolated bovine adrenal medullary cells in culture. Four-day treatment of cells with 8-bromo-cyclic AMP (10(-3) M) an analogue of cAMP, or forskolin (10(-5) M), an activator of adenylate cyclase, decreased soluble [3H]dexamethasone binding by 55 and 54%, respectively. 8-Bromo-cyclic GMP treatment decreased [3H]dexamethasone binding by 31 and 34% at 10(-5) and 10(-4) M, respectively. Treatment with 8-bromo-cyclic AMP or forskolin, but not 8-bromo-cyclic GMP, elevated cortisol levels in the medium of treated cells, presumably by elevating steroidogenesis in contaminating cortical cells. Cultures further purified to produce chromaffin-enriched cell cultures, also showed a loss (41%) in soluble [3H]dexamethasone binding when treated with 8-bromo-cyclic AMP (10(-3) M). Four-day treatment of standard Percoll-isolated cells with low concentrations of cortisol (10(-9) to 2 x 10(-7) M) similar to that found in the medium of 8-bromo-cyclic AMP-treated cells, did not decrease soluble [3H]dexamethasone binding, whereas higher cortisol concentrations (10(-6) M) produced a 62% loss in soluble binding. Adsorption of cortisol with bovine serum albumin (5 mg/ml) prevented a cortisol (10(-6) M)-induced loss in soluble [3H]dexamethasone binding with no effect on the 8-bromo-cyclic AMP-induced loss in binding, suggesting that the decrease in binding observed following 8-bromo-cyclic AMP treatment is not due to the release of cortisol from contaminating cortical cells. Finally, we report a loss in the ability of 8-bromo-cyclic AMP- or 8-bromo-cyclic GMP-treated cells to fully induce the activity of phenylethanolamine N-methyltransferase in response to cortisol, indicating that decreases in soluble [3H]dexamethasone binding translate into a decrease in the functional consequence of glucocorticoid receptor binding in adrenal medullary cells. In conclusion, these results indicate that long-term increases in cyclic nucleotide second messengers are able to decrease glucocorticoid receptor binding in bovine adrenal medullary cells, via a mechanism independent of released cortisol.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Interleukin-2 modulates evoked release of [3H]dopamine in rat cultured mesencephalic cells.

Mesencephalic cell cultures were used as a model to investigate the effects of interleukin-2 (IL-2) on evoked release of [3H]dopamine ([3H]DA) and gamma-[3H]-aminobutyric acid ([3H]GABA). At low concentrations (10(-13)-10(-12) M), IL-2 potentiated [3H]DA release evoked by the excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate, whereas higher IL-2 concentrations (10(-9)-10(-8) M) had no effect. IL-2 (10(-14)-10(-8) M) modulated K(+)-evoked [3H]DA release in a biphasic manner, with low concentrations (10(-12)-10(-11) M) of IL-2 potentiating and higher concentrations (10(-9)-10(-8) M) inhibiting K(+)-induced [3H]DA release. IL-2 (10(-14)-10(-8) M) by itself failed to alter spontaneous [3H]DA release. The inhibition by IL-2 of K(+)-evoked [3H]DA release was reversible and not due to neurotoxicity, as preexposure to IL-2 (10(-8) M) had no significant effect on the subsequent ability of dopaminergic cells to take up and to release [3H]DA. Under our experimental conditions, IL-2 (10(-8) M) did not alter Ca(2+)-independent [3H]GABA release evoked by either K+ or NMDA. The results of this study indicate that IL-2 is able to potentiate [3H]DA release evoked by a number of different stimuli, including K+ depolarization and activation of both NMDA and non-NMDA receptor subtypes in mesencephalic cell cultures. IL-2 is active at very low concentrations, a finding that indicates a potent effect of IL-2 on dopaminergic neurons and implicates a physiological role for this cytokine in the modulation of DA release.

Animals↗
PubMed1992

Effects of L- and N-type Ca2+ channel antagonists on excitatory amino acid-evoked dopamine release.

In the present study we tested the effect of dihydropyridine (DHP) Ca2+ channel antagonists and of omega-conotoxin GVIA on [3H]dopamine (DA) release evoked by the activation of excitatory amino acid (EAA) receptors in cultures of fetal rat ventral mesencephalon, in order to investigate the role of voltage-sensitive L- and N-type Ca2+ channels in these EAA-mediated processes. Micromolar concentrations (10-30 microM) of DHP L-type Ca2+ channel antagonists inhibited [3H]DA release evoked by N-methyl-D-aspartate (NMDA), kainate, quisqualate or veratridine. [3H]DA release evoked by the L-type Ca2+ channel agonist, Bay K 8644, was inhibited by lower concentrations (0.1-1 microM) of the DHP antagonist, nitrendipine, than was the release evoked by EAAs. The DHP antagonist, (+)-PN 200-110, was more potent than (-)-PN 200-110 in inhibiting [3H]DA release evoked by Bay K 8644, but the two stereoisomers were equipotent in inhibiting NMDA-evoked release. These results indicate that activation of L-type Ca2+ channels is able to evoke [3H]DA release. However activation of L-type channels is not involved in EAA-induced [3H]DA release and therefore inhibition of EAA-induced [3H]DA release by micromolar concentrations of DHPs must be mediated by actions other than inhibition of L-type Ca2+ channels. omega-Conotoxin GVIA (3 microM) had no effect on [3H]DA release evoked by Bay K 8644, indicating that the toxin may selectively inhibit N-type channels in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Alterations in spinal cord excitatory amino acid receptors in amyotrophic lateral sclerosis patients.

Excitatory amino acids (EAA) have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We have analyzed the distribution of the N-methyl-D-aspartate (NMDA) 1-(1-(2-thienyl)-cyclohexyl) piperidine (TCP), kainate and alpha-amino-3-hydroxy-5-methyl-4 isoxazole propionic acid (AMPA) quisqualate subtypes of EAA receptors using quantitative receptor autoradiography in the cervical and thoracic spinal cords of patients who have died with ALS, and of controls. We observed that in control spinal cords [3H]TCP/NMDA binding sites were located both in the ventral and dorsal horns with the highest densities being situated in lamina II. [3H]AMPA and [3H]kainate binding sites were present almost exclusively in the substantia gelatinosa of the dorsal horn. In ALS, the distribution of these 3 types of receptors was unchanged, but [3H]TCP/NMDA binding was decreased both in the dorsal and ventral horns. [3H]kainate binding was possibly decreased in substantia gelatinosa, of ALS cords. However, the limited sample size available for [3H]kainate binding did not permit statistical analysis. [3H]AMPA binding sites were unaltered in ALS. These results indicate that there is a preferential reduction in NMDA receptors in ALS. We suggest that should an excitotoxic mechanism be involved in the pathogenesis of ALS, then NMDA receptors may be the target of this effect.

Adult↗