RESUMEN
Tolerance, manifested by a diminished electroencephalographic response at cortical and subcortical recording sites, was found in rats subjected to repeated systemic injections of morphine sulfate. Reversal of tolerance to morphine resulted from destruction of the medial thalamus.
Asunto(s)
Tolerancia a Medicamentos/efectos de los fármacos , Electroencefalografía , Morfina/farmacología , Tálamo/fisiología , Animales , Conducta Animal/efectos de los fármacos , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/fisiología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Relación Dosis-Respuesta a Droga , Hipocampo/fisiología , Humanos , Inyecciones Intraperitoneales , Masculino , Actividad Motora/efectos de los fármacos , Naloxona/administración & dosificación , Naloxona/farmacología , Ratas , Síndrome de Abstinencia a Sustancias , Tálamo/efectos de los fármacosRESUMEN
Single doses of ethanol a severe depletion (95 percent) of cerebellar guanosine 3',5' -cyclic monophosphate (cyclic GMP) within 1 hour after administration. The degree of this depletion is dose-dependent and is a function of the amount of ethanol in the blood. Interactions between ethanol and cyclic GMP may account for some of the intoxicating properties of ethanol.
Asunto(s)
Cerebelo/efectos de los fármacos , GMP Cíclico/metabolismo , Etanol/farmacología , Animales , Cerebelo/metabolismo , Masculino , Ratas , Factores de TiempoRESUMEN
The chromatographic separation and biochemical characterization of a beta-bungarotoxin is described. This toxin is isolated as the most basic eluting protein of Bungarus multicinctus venom when separated by column chromatography on CM-Sephadex C-25. The protein migrated as a single band on pH 4.3 and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The molecular weight of this toxin was estimated to be 10 000 +/- 1000 by analytical sedimentation analysis. This value was consistent with the electrophoretic mobility of the toxin in SDS-polyacrylamide gels. The amino acid composition of this 11 000-dalton beta-bungarotoxin was similar to that of the 22 000-dalton beta-bungarotoxin previously reported (Lee et al. (1972) J. Chromatogr. 72, 71--82; Kelly, R.B. and Brown, III, F.R. (1974) J. Neurobiol. 5, 135--150; Kondo et al. (1978) J. Biochem. Tokyo 83, 91--99), suggesting that the 11 000-dalton toxin may be one of the polypeptide chains of the larger toxin. The 11 000-dalton beta-bungarotoxin was toxic to mice when injected intravenously. Animals that received lethal doses exhibited hyperexcitability followed by ataxia, convulsions, and death. The minimum lethal dose was 0.12 microgram/g body weight. This beta-bungarotoxin exhibited Ca2+-dependent phospholipase A activity comparable to that of the 22 000-dalton beta-bungarotoxin. The enzyme exhibited phospholipid substrate specificity in the rank order of phosphatidyl-choline, phosphatidylserine, phosphatidylethanolamine, and phosphatidyl-inositol. The enzyme activity was destroyed by boiling for 3 min at pH 8.6. In addition, an enzymatically inactive quantity of the 11 000-dalton toxin, equivalent to five times the minimum lethal dose of enzymatically active toxin, was not lethal when injected into mice. To test whether phospholipase A activity is responsible for lethality, bee venom phospholipase A2 was injected into mice at similar and greater concentrations with no toxic effect. Thus, while phospholipase A activity may be required for the lethal effect of the 11 000-dalton beta-bungarotoxin, the specificity of action of the toxin is not determined by its enzyme activity.
Asunto(s)
Bungarotoxinas/aislamiento & purificación , Aminoácidos/análisis , Animales , Conducta Animal/efectos de los fármacos , Bungarotoxinas/metabolismo , Bungarotoxinas/toxicidad , Calcio/farmacología , Humanos , Cinética , Ratones , Peso Molecular , Fosfolipasas/metabolismoRESUMEN
To investigate the role of the Ca2+-binding protein calmodulin on histamine release in the rat peritoneal mast cell, we exposed cells to exogenous calmodulin in the presence of a variety of histamine secretagogues. Histamine release stimulated by compound 48/80, polymyxin B and ionophore A23187 was inhibited while concanavalin A-stimulated release was not affected. Calmodulin in the presence of the secretagogues did not affect cell viability and calmodulin alone had no effect on histamine release. No direct interaction between calmodulin and the secretagogues was observed. Exogenous calmodulin does not appear to be incorporated into the cell. The inhibition of histamine release by calmodulin can be explained as a labile interaction between the protein and the cell that requires externally-bound Ca2+. These experiments demonstrate the use of exogenous calmodulin as a probe in the study of the mechanism of histamine release.
Asunto(s)
Calmodulina/farmacología , Liberación de Histamina/efectos de los fármacos , Mastocitos/inmunología , Animales , Calcimicina/farmacología , Calcio/farmacología , Concanavalina A/farmacología , Ácido Egtácico/farmacología , Cinética , Masculino , Mastocitos/efectos de los fármacos , Polimixina B/farmacología , Ratas , Ratas Endogámicas , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
The radioprotectant WR 2721 administered intraperitoneally to rats at 30--40 min before exposure to 1000 rad of 60Co caused a reduction in spleen lysosomal enzyme activity and fluctuations in cyclic nucleotide levels. Liver and spleen cAMP levels from drug-treated animals were higher at 3--6 hr postirradiation whereas spleen cGMP levels were lower at 1--4 hr postirradiation than irradiated controls not given the radioprotectant. At 3 days after radiation exposure, spleen cyclic nucleotide levels and lysosomal enzyme activities in rats given WR 2721 were closer to the level of nonirradiated control rats than of irradiated rats receiving saline.
Asunto(s)
Amifostina/farmacología , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Lisosomas/enzimología , Compuestos Organotiofosforados/farmacología , Animales , AMP Cíclico/efectos de la radiación , GMP Cíclico/efectos de la radiación , Glucuronidasa/metabolismo , Hígado/enzimología , Lisosomas/efectos de la radiación , Masculino , Ratas , Ratas Endogámicas , Bazo/enzimología , Bazo/efectos de la radiación , Factores de TiempoRESUMEN
Within 1 hr after ip injection of the radioprotectant WR 2721 into rats, splenic cGMP levels dropped and remained suppressed for 6 hr before returning to normal. However, if rats were exposed to ionizing radiation 30-40 min after WR 2721 treatment, they had higher cGMP levels at 3 hr postirradiation than the nonirradiated, drug-treated controls, but the cGMP content was still found to be lower than that of the irradiated nondrug-treated controls. Radiation exposure of animals pretreated with WR 2721 also resulted in higher liver and spleen levels of cAMP and additional elevations in spleen prostaglandin content, compared with irradiated controls at 3-6 hr after radiation treatment. The secondary fluctuations of lysosomal enzyme activities, prostaglandin content, and cyclic nucleotide levels were also altered in irradiated rats pretreated with WR 2721 when compared with irradiated controls. Liver and spleen lysosomal beta-glucuronidase activities, spleen cAMP and cGMP levels, and spleen prostaglandin concentrations were closer to physiological levels at 3 days postirradiation in rats given WR 2721 before the radiation treatment.
Asunto(s)
Amifostina/farmacología , Lisosomas/enzimología , Nucleótidos Cíclicos/metabolismo , Compuestos Organotiofosforados/farmacología , Prostaglandinas/metabolismo , Animales , AMP Cíclico/análisis , GMP Cíclico/análisis , Glucuronidasa/análisis , Membranas Intracelulares/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Endogámicas , Bazo/metabolismo , Factores de Tiempo , Irradiación Corporal TotalRESUMEN
Lipoic acid is a lipophilic antioxidant that participates in many enzymatic reactions and is used clinically to treat mushroom poisoning and metal toxicity. In this report the protective effect of lipoic acid (oxidized form) against radiation injury to hematopoietic tissues in mice was assessed by the endogenous and exogenous spleen colony assays and survival (LD50/30) assay. Intraperitoneal administration of lipoic acid at a nonlethal concentration of 200 mg/kg body wt, 30 min before irradiation increased the LD50/30 from 8.67 to 10.93 Gy in male CD2F1 mice. Following a 9-Gy irradiation, the yield of endogenous spleen colony-forming units in mice treated with saline and lipoic acid was 0.75 +/- 0.5 and 8.9 +/- 1.6, respectively. Using the exogenous spleen colony assay, lipoic acid treatment increased the D0 from 0.81 +/- 0.01 to 1.09 +/- 0.01 Gy, yielding a dose modification factor of 1.34 +/- 0.01. Dihydrolipoic acid (reduced form) has no radioprotective effect in CD2F1 mice.
Asunto(s)
Células Madre Hematopoyéticas/efectos de la radiación , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Ácido Tióctico/uso terapéutico , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ensayo de Unidades Formadoras de Colonias , Células Madre Hematopoyéticas/efectos de los fármacos , Masculino , Ratones , Traumatismos Experimentales por Radiación/mortalidadRESUMEN
The effect of 60Co gamma radiation on DNA methylation was studied in four cultured cell lines. In all cases a dose-dependent decrease in 5-methylcytosine was observed at 24, 48, and 72 h postexposure to 0.5-10 Gy. Nuclear DNA methyltransferase activity decreased while cytoplasmic activity increased in irradiated (10 Gy) V79A03 cells as compared to controls. No DNA demethylase activity was detected in the nuclei of control or irradiated V79A03 cells. Additionally, gamma radiation resulted in the differentiation of C-1300 N1E-115 cells, a mouse neuroblastoma line, in a dose- and time-dependent manner. These results are consistent with the hypothesis that (1) genes may be turned on following radiation via a mechanism involving hypomethylation of cytosine and (2) radiation-induced hypomethylation results from decreased intranuclear levels of DNA methyltransferase.
Asunto(s)
ADN/efectos de la radiación , Metiltransferasas/metabolismo , 5-Metilcitosina , Animales , Línea Celular , Radioisótopos de Cobalto , Citosina/análogos & derivados , Citosina/metabolismo , ADN/metabolismo , ADN de Neoplasias/metabolismo , ADN de Neoplasias/efectos de la radiación , Rayos gamma , Humanos , MetilaciónRESUMEN
At 1 hr to 14 days after total-body exposure of guinea pigs to 3.0 Gy 60Co, changes were detected in prostaglandin concentrations in bronchial airway tissues. At 3 hr postexposure, tissue levels of PGE were significantly elevated, while at 48 hr transiently elevated levels of PGF2 alpha were observed. By 72 hr, levels returned to control values. Airway synthesis of thromboxane B2 in irradiated animals did not differ from that in controls. Also assessed were the capacities of bronchial airway preparations to respond to H-1 receptor stimulation by the exogenous addition of histamine or transmembrane divalent cation transport stimulation with ionophore. Tissues from irradiated animals demonstrated alterations in the amount and type of prostaglandins generated, varying with time postirradiation.
Asunto(s)
Pulmón/efectos de la radiación , Prostaglandinas E/biosíntesis , Prostaglandinas F/biosíntesis , Tromboxano B2/biosíntesis , Tromboxanos/biosíntesis , Animales , Calcimicina/farmacología , Dinoprost , Rayos gamma , Cobayas , Histamina/farmacología , Pulmón/metabolismo , Masculino , Prostaglandinas E/análisis , Prostaglandinas F/análisis , Traumatismos por Radiación/metabolismo , Radioinmunoensayo , Receptores Histamínicos H1/metabolismo , Tromboxano B2/análisis , Factores de Tiempo , Irradiación Corporal TotalRESUMEN
Diamine oxidase (DAO; EC 1.4.3.6) activity was measured in plasma and in ileal tissue homogenates prepared from male Sprague-Dawley rats euthanized at 1-15 days after acute whole-body irradiation with 14.5-MeV electrons. Animals irradiated with 1 Gy showed no diminution in plasma and ileal DAO activities through Day 13 relative to nonirradiated controls. Animals irradiated with 5, 10, and 12 Gy displayed marked declines in ileal DAO activity, with levels reaching a nadir on Day 3. This was paralleled by a decrease in plasma DAO activity in all three dose groups. Recovery of ileal and plasma DAO levels was later seen as early as Day 4 in animals irradiated with 5- and 10-Gy doses, but animals receiving 12 Gy did not survive beyond Day 3. The relationship between radiation dose and levels of plasma and ileal DAO on Day 3, the time of maximum decrease at all doses, was also investigated. Ileal DAO activity decreased almost linearly between 2 and 8 Gy. Plasma DAO activity closely paralleled the dose dependency of the ileal levels. These data suggest that plasma DAO activity might be useful as a biologic marker of intestinal epithelial injury and recovery after acute radiation exposure.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/efectos de la radiación , Intestino Delgado/enzimología , Animales , Relación Dosis-Respuesta en la Radiación , Mucosa Intestinal/enzimología , Mucosa Intestinal/efectos de la radiación , Intestino Delgado/efectos de la radiación , Masculino , Ratas , Ratas Endogámicas , Irradiación Corporal TotalRESUMEN
Exposure of pentobarbital-anesthetized rats to 14.5-MeV electrons results in radiation-induced physiological dysfunction. Responses include transient hypotension, a transient decrease in heart rate, respiratory dysrhythmias, and a prolonged increase in pulse pressure. Magnitudes of these responses are dose related, and maximal responses can be elicited by either whole- or partial-body (head or abdominal) exposure to 10,000 rad. These responses were associated with a fivefold increase in arterial plasma concentration of epinephrine, whereas histamine, norepinephrine, and beta-endorphin did not change during the first minute after the onset of exposure. Administration of diphenhydramine, a histamine receptor antagonist, resulted in a significant decline of baseline cardiovascular function and inhibited radiation-induced cardiovascular dysfunction. The diphenhydramine-induced decrease in preexposure blood pressure was reversed by angiotensin infusion, but this procedure failed to restore the mechanism(s) responsible for the cardiovascular responses to radiation. Results of these experiments and information available in the literature support the hypothesis that these responses are due to an interference in the autonomic pathways that modulate cardiovascular function.
Asunto(s)
Anestesia , Pentobarbital , Traumatismos Experimentales por Radiación/fisiopatología , Animales , Presión Sanguínea/efectos de la radiación , Electrones , Endorfinas/sangre , Epinefrina/sangre , Frecuencia Cardíaca/efectos de la radiación , Histamina/sangre , Antagonistas de los Receptores Histamínicos/uso terapéutico , Masculino , Norepinefrina/sangre , Pulso Arterial/efectos de la radiación , Traumatismos Experimentales por Radiación/prevención & control , Ratas , Ratas Endogámicas , Respiración/efectos de la radiación , betaendorfinaRESUMEN
Prostaglandin E1 (PGE1)-stimulated [3H]3',5'-cyclic adenosine monophosphate ([3H]cAMP) accumulation was studied in a rat brain mince system to determine if stimulation of net [3H]cAMP accumulation could be prevented or reversed by morphine. Incubated minces of whole brain minus cerebellum were prepared from naive, acutely morphine-treated, and morphine-tolerant and withdrawing rats. Basal levels of [3H]cAMP accumulation in the three groups were equal within experimental limits. Morphine addition to the PGE1-stimulated minces did not prevent or reverse stimulation of [3H]cAMP accumulation in any of the three experimental groups. The data do not support the thesis that PGE1-stimulated cAMP accumulation in brain is a locus of opiate action in the phenomena of opiate analgesia, tolerance, and dependence.
Asunto(s)
Encéfalo/efectos de los fármacos , AMP Cíclico/metabolismo , Prostaglandinas E/farmacología , Animales , Encéfalo/metabolismo , Tolerancia a Medicamentos , Humanos , Masculino , Morfina/farmacología , Dependencia de Morfina/metabolismo , Naloxona , Ratas , Síndrome de Abstinencia a Sustancias/inducido químicamenteRESUMEN
Beta-adrenergic receptors were characterized by measuring the specific binding of 3H-dihydroalprenolol (DHA) on intact isolated rat peritoneal mast cells (RPMC) and on perigranular membranes derived from purified RPMC granules. The specific binding of 3H-DHA reaches an equilibrium within 30 min at 5 degrees C and is linear with cell number. Scatchard analysis reveals two populations of binding sites on intact cells: with KD = 10.6 +/- 2.6 and 129 +/- 4.7 nM and Bmax of 186 +/- 38 and 1200 +/- 415 fmol/10(6) cells, respectively. Each cell contains 120 X 10(3) high-affinity binding sites and 720 X 10(3) low-affinity binding sites. There appears to be neither alpha-adrenergic nor muscarinic cholinergic receptors on the RPMC. Specific binding of 3H-DHA also occurred to isolated granules with perigranular membranes. The binding was saturable with a single population of binding sites with an affinity (KD) of 7.0 +/- 0.45 nM. Maximum binding (Bmax) was calculated at 56.6 +/- 1.9 fmol/10(9) granules. Subfractionation of granule components demonstrated that the specific binding sites appear to be localized exclusively on the perigranular membrane.
Asunto(s)
Mastocitos/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores Adrenérgicos/metabolismo , Animales , Líquido Ascítico/citología , Membrana Celular/metabolismo , Dihidroalprenolol/metabolismo , Dihidroergotoxina/metabolismo , Cinética , Masculino , Quinuclidinil Bencilato/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Dose-related alterations in the levels of prostaglandins (PGF2 alpha and PGE) and thromboxane B2 (TxB2) were observed in the urine of unanesthetized rats following whole-body gamma radiation. Exposure doses of 100 and 900 rads resulted in significant changes in urinary levels of these cyclooxygenase products. These findings suggest the potential use of radioimmunoassay measurement of urinary prostaglandins and thromboxane as a noninvasive indicator of radiation exposure.
Asunto(s)
Prostaglandinas E/orina , Prostaglandinas F/orina , Tromboxano B2/orina , Tromboxanos/orina , Irradiación Corporal Total , Animales , Dinoprost , Relación Dosis-Respuesta en la Radiación , Masculino , Radioinmunoensayo , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The role of cellular membranes in thymocyte apoptosis has been examined. Trolox, a water soluble analogue of vitamin E and inhibitor of membrane damage, inhibits DNA fragmentation in thymocytes exposed to gamma-radiation. Trolox is most effective in inhibiting DNA fragmentation when added to cells within 30 min post-irradiation. Exposure to trolox only during irradiation did not prevent DNA fragmentation, suggesting that it does not work by scavenging free radicals generated during radiation exposure. Incubation of the irradiated cell suspension with trolox for 2 h post-irradiation was sufficient to prevent DNA fragmentation measured at 24 h in irradiated cells. This suggests that trolox irreversibly inhibits a cellular lesion required for apoptosis. The induction of DNA fragmentation appears to be related to a concurrent, pronounced flow of Ca2+ into the cell. At 3 h post-irradiation the amount of Ca2+ in irradiated thymocytes was more than twice that of unirradiated thymocytes. Membrane damage has been shown to affect the transport of Ca2+. Trolox treatment completely blocked the radiation-induced influx of Ca2+ into the thymocytes. These results suggest that membrane damage is a critical lesion that is involved in DNA fragmentation in thymocyte apoptosis.
Asunto(s)
Apoptosis/fisiología , Membrana Celular/fisiología , Linfocitos/efectos de la radiación , Timo/citología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Membrana Celular/efectos de los fármacos , Membrana Celular/efectos de la radiación , Cromanos/uso terapéutico , Radioisótopos de Cobalto , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Rayos gamma , Técnicas In Vitro , Linfocitos/efectos de los fármacos , Masculino , Ratones , Vitamina E/análogos & derivadosRESUMEN
5-Azacytidine and sodium butyrate, two DNA methylation-disrupting agents, were tested for radioprotective properties on V79A03 cells. Both compounds can activate genes not previously expressed (e.g. metallothionein). 5-Azacytidine treatment (3 microM, 24 h) caused a 50% decrease in the 5-methylcytosine content of V79A03 DNA whereas sodium butyrate treatment (1 mM, 24h) resulted in a 700% increase in 5-methylcytosine content. Additionally, 5-azacytidine treatment resulted in the increased survival of V79A03 cells, with treatment 24 h prior to exposure to gamma radiation providing a dose reduction factor of 1.8. Sodium butyrate treatment did not result in a significant increase in survival. These results indicate that the hypomethylation of genomic DNA prior to exposure to gamma radiation correlates with an increase in survival of V79A03 cells, possibly due to the activation of the enzymes involved in repair.
Asunto(s)
Azacitidina/farmacología , Butiratos/farmacología , Protectores contra Radiación/farmacología , 5-Metilcitosina , Animales , Ácido Butírico , Supervivencia Celular/efectos de la radiación , Citosina/análogos & derivados , Citosina/metabolismo , ADN/metabolismo , Depresión Química , Técnicas In Vitro , Metilación , Estimulación QuímicaRESUMEN
Circadian rhythms in noradrenergic (NE) and dopaminergic (DA) metabolites and in cyclic nucleotide production were measured in discrete regions of rat brain. A circadian rhythm was found in the concentration of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in the hippocampus. No MHPG rhythm was found in frontal, cingulate, parietal, piriform, insular or temporal cortex, or in hypothalamus. Circadian rhythms in the concentration of the NE metabolite, 3,4-dihydroxyphenylglycol (DHPG), occurred in occipital and parietal cortex and hypothalamus, with no rhythm observable in temporal or insular cortex, hippocampus, pons-medulla or cerebellum. The 24-hr mean concentration of MHPG varied 3.5-fold, highest in cingulate and lowest in parietal, temporal and occipital cortex. The 24-hr mean concentration of DHPG varied 6-fold, highest in hypothalamus and lowest in parietal cortex. Circadian rhythms in the concentration of the DA metabolite, homovanillic acid (HVA), were found in olfactory tubercle, amygdala and caudate-putamen, but not in nucleus accumbens. A circadian rhythm in the concentration of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), occurred in nucleus accumbens, but not in olfactory tubercle or caudate-putamen. The mean 24-hr concentration of HVA was highest in caudate-putamen, intermediate in nucleus accumbens, and lowest in olfactory tubercle and amygdala. The mean 24-hr concentration of DOPAC was highest in nucleus accumbens and lower in olfactory tubercle and caudate-putamen. Circadian rhythms were found in the concentration of cyclic GMP (cGMP) in all regions measured except parietal cortex. The mean 24-hr concentration varied 128-fold, highest in nucleus accumbens, frontal poles, and hypothalamus and lowest in cingulate cortex. Circadian rhythms in cyclic AMP (cAMP) concentration were found in piriform, temporal, occipital, cingulate, and parietal cortex, amygdala and nucleus accumbens. No rhythms were found in frontal or insular cortex, hypothalamus, hippocampus, caudate-putamen or olfactory tubercle. The 24-hr mean cAMP concentration varied 4-fold, highest in parietal cortex and lowest in caudate-putamen and amygdala. Norepinephrine metabolites and dopamine metabolites were rhythmic in few regions. It is, therefore, unlikely that the rhythmicity measured in adrenergic receptors is, in general, a response to rhythmic changes in adrenergic transmitter release. The putative second messenger response systems, especially cGMP, were more often rhythmic. The rhythms in cGMP are parallel in form and region to those in the alpha 1-adrenergic receptor and may act as 2nd messenger for that receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Catecolaminas/metabolismo , Ritmo Circadiano , Nucleótidos Cíclicos/biosíntesis , Animales , Encéfalo/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Dopamina/metabolismo , Metoxihidroxifenilglicol/análogos & derivados , Metoxihidroxifenilglicol/metabolismo , Norepinefrina/metabolismo , Ratas , Distribución TisularRESUMEN
Cerebrospinal fluid (CSF) histidine concentration was significantly elevated in seven patients early in the alcohol withdrawal syndrome (206.3 +/- 74.4 (SEM) nanomols/ml CSF). When these same patients were restudied an average of six days later when alcohol withdrawal was clinically resolved, their mean CSF histidine concentration continued to be significantly elevated (164.7 +/- 24.7) when compared to normal (12.0 +/- 0.5 nanomols/ml CSF). Other amino acids (aspartic acid, serine, alanine, methionine, leucine, tyrosine, phenylalanine, lysine and arginine) showed no definite changes from normal, and no change during the course of alcohol withdrawal. Possible reasons for these high concentrations and the extreme variability (especially early in alcohol withdrawal) are discussed.