Role of Bcl-2 in alpha beta T cell development in mice deficient in the common cytokine receptor gamma-chain: the requirement for Bcl-2 differs depending on the TCR/MHC affinity

Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were selectively bred to have severe (WSP) or mild (WSR) handling-induced convulsions after chronic ethanol inhalation. The purpose of the present experiments was to determine whether seizure susceptibility differences between WSP and WSR mice during ethanol withdrawal were specific to agents acting at gamma-aminobutyric acidA or excitatory amino acid (EAA) receptors. Male WSP and WSR mice were exposed to ethanol vapor or air for 24 or 72 h. During peak withdrawal (i.e., between 6.5 and 8 h after removal from the inhalation chambers), separate groups of animals were administered pentylenetetrazol, (+)bicuculline, N-methyl-D-aspartate, kainic acid, or strychnine via timed tail vein infusion. Withdrawal from ethanol significantly increased sensitivity to pentylenetetrazol and (+)bicuculline versus air-exposed WSP and WSR mice. In contrast, sensitivity to N-methyl-D-aspartate-induced convulsions was significantly decreased in the ethanol-exposed WSR and unchanged in the ethanol-exposed WSP mice. Sensitivity to kainic acid was significantly increased in both ethanol-exposed WSR and WSP mice, although the magnitude of change in sensitivity was greater in the ethanol-withdrawing WSP line. Interestingly, sensitivity to strychnine was decreased similarly in the ethanol-exposed WSP and WSR mice, compared with their respective air-exposed animals. These results suggest that chronic ethanol increased sensitivity to convulsants active at gamma-aminobutyric acidA receptors similarly in WSP and WSR mice, but differentially changed sensitivity to convulsants active at EAA receptors in the lines. This supports a role for EAA systems in determining genetic susceptibility to alcohol withdrawal.     

Sensitivity to N-methyl-D-aspartic acid-induced convulsions is genetically associated with resistance to ethanol withdrawal seizures

Mice genetically selected to be resistant (withdrawal-seizure resistant, WSR) or prone (withdrawal-seizure prone, WSP) to handling-induced convulsions during ethanol withdrawal were tested for sensitivity to convulsions induced by timed intravenous (i.v.) infusion of N-methyl-D-aspartic acid (NMDA). WSR mice displayed convulsions at infused doses of NMDA that averaged 20% lower than WSP mice. This result was present in both genetically independent replicates of the WSR and WSP mice and provides strong evidence for an involvement of the NMDA system in the difference in withdrawal seizures present in these lines.     

Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.

Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 ± 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Similar responses by macrophages from young and old mice infected with Mycobacterium tuberculosis

Repeated ethanol withdrawal experience has been shown to result in exacerbated seizures associated with future withdrawal episodes. This sensitization of the withdrawal response has been postulated to represent a "kindling" phenomenon. The present study employed an established model of repeated ethanol withdrawals to examine the potential role of GABA(A), and NMDA and non-NMDA glutamate receptor systems in mediating enhanced seizure activity, as assessed by sensitivity to seizures induced by pentylenetetrazol (PTZ), NMDA, and kainic acid (KA) i.v. infusions, respectively. Adult C3H mice were chronically exposed to ethanol vapor in inhalation chambers. A multiple withdrawal (MW) group received four cycles of 16-h ethanol vapor exposure interrupted by 8-h periods of abstinence; a single withdrawal (SW) group was tested after a single 16-h bout of ethanol intoxication; and the third group was ethanol-naive, serving as controls (C). Results indicated that the MW group evidenced significantly lower PTZ and NMDA seizure thresholds compared to SW and C groups at 8 and 24 h post-withdrawal. In contrast, MW and SW groups exhibited reduced sensitivity (higher seizure threshold) to KA in comparison to controls, and this effect only emerged at 24 h post-withdrawal. Further, MW mice required significantly less additional PTZ or NMDA to induce more severe convulsions once initial signs of seizures were elicited. Conversely, latency and amount of KA required to transition from initial seizure signs to more severe end-stage convulsions was significantly greater for MW and SW groups compared to controls. Taken together, these results suggest that repeated ethanol withdrawal experience does not result in a global non-specific lowering of threshold to convulsive stimuli, but rather, selective changes in CNS mechanisms associated with neural excitability may underlie potentiated withdrawal responses. Thus, reduced GABA(A) receptor function and increased NMDA receptor activity may become exaggerated as a consequence of repeated withdrawal experience, while reduced sensitivity to KA induced seizures may represent a compensatory response to withdrawal-related CNS hyperexcitability.     

Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.     

Sensitivity to low doses of ethanol and pentobarbital in mice selected for sensitivity to hypnotic doses of ethanol.

Assessed sensitivity to low doses of ethanol and pentobarbital in mice that had been selectively bred with respect to ethanol sleep time (the length of time an animal remains on its back following a hypnotic dose of ethanol). The hypothesis investigated was that short-sleep (SS) Ss might be more sensitive than long-sleep (LS) Ss to excitatory effects produced by low doses of depressants. In support of this hypothesis, SS Ss were more active in an open-field test after ethanol than were LS Ss. Two experiments were conducted, using 88 LS and 88 SS Ss. The lines did not differ in performance on a rotating-rod apparatus after these same doses of ethanol, suggesting that the difference in open-field activity was not attributable to a greater impairment of locomotor activity in LS Ss. A similar difference in the open-field activity of the selected lines was observed with pentobarbital. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correction to Ardayfio and Kim (2006).

Reports an error in "Anxiogenic-Like Effect of Chronic Corticosterone in the Light-Dark Emergence Task in Mice" by Paul Ardayfio and Kwang-Soo Kim (Behavioral Neuroscience, 2006[Apr], Vol 120[2], 249-256). In the article "Anxiogenic-Like Effect of Chronic Corticosterone in the Light-Dark Emergence Task in Mice," by Paul Ardayfio and Kwang-Soo Kim (Behaviorial Neuroscience, 2006, Vol. 120, No. 2, pp. 249-256), the measurement unit of the corticosterone concentration on p. 250 (under the Drugs heading) was incorrect. The correct unit is μg/ml. The corrected sentence follows: "Corticosterone (Sigma, St. Louis, MO) was dissolved in ethanol, diluted, and administered via the drinking water at a final concentration of 0 or 35 μg/ml in 0.3% ethanol." (The following abstract of the original article appeared in record 2006-05348-003.) Chronic hypercortisolemia is a hallmark of neuroendocrine and psychiatric disorders, such as Cushing's disease and depression. Whether cortisol directly contributes to the altered mood and anxiety symptoms seen in these diseases remains unclear. To address this, the authors have modeled hypercortisolemia by administering corticosterone in the drinking water of female Swiss Webster mice for 17 or 18 days (13 mg/kg). Light-dark emergence, startle habituation, and startle reactivity were measured. Chronic but not acute treatment with corticosterone increased the latency to emerge into the light compartment, an anxiogenic-like effect. Chronic corticosterone treatment did not affect startle habituation, but did reduce startle reactivity. This study suggests that chronic hypercortisolemia may contribute to anxiety-related behavior in patients with Cushing's disease and depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electroencephalographic correlates of audiogenic seizures during ethanol withdrawal in mice

C57BL/6Bg mice had silver bead electrodes chronically implanted on the surface of the cortex and had their cortical EEG recorded during audiogenic seizures following ethanol withdrawal. For 7 days, the experimental groups were fed a liquid diet containing 6% v/v ethanol ad lib as the only source of food and water. The control group was fed a similar diet containing an isocaloric amount of sucrose. The cortical EEG's of experimental and control groups before, during, and after treatment were virtually identical. Only the experimental group was susceptible to audiogenic seizures. During audiogenic seizures, the cortical EEG showed no sign of spike waves or paroxysmal activity. This is in contrast to picrotoxin convulsions with these same mice as well as to spontaneous convulsions in animals following ethanol withdrawal. Similar EEG observations have been reported on audiogenic seizures from genetic and acoustically primed susceptibilities. Consequently, we suggest that all audiogenic seizure responses, including those during ethanol withdrawal, are a type of subcortical epilepsy.     

Structure and expression of bombyxin E1 gene: a novel family gene that encodes bombyxin-IV, an insect insulin-related neurosecretory peptide

Comparison was made of the ability of two dihydropyridine calcium channel antagonists, nitrendipine and felodipine, to prevent a range of signs of ethanol withdrawal. The increases in handling-induced behavior seen in mice during withdrawal from chronic ethanol treatment were prevented by administration of nitrendipine, 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a similar displacement of dihydropyridine binding in central nervous system tissue, in vivo and in vitro. A higher dose of felodipine, 20 mg/kg, also had no effects. Nitrendipine, but not felodipine, prevented audiogenic seizures during the withdrawal phase. Similarly, nitrendipine prevented both the decrease in thresholds for N-methyl-DL-aspartate seizures and the increase in thresholds for convulsions due to 4-aminopyridine, which were seen during the withdrawal period, while felodipine did not alter either of these changes. Withdrawal from the ethanol chronic treatment increased the thresholds to seizures produced by intravenous aminophylline; this change was also prevented by nitrendipine. The significance of this increase in thresholds was lost after felodipine administration. In naive mice (not treated with ethanol) the doses of nitrendipine and felodipine used in the withdrawal studies were tested against the effects of convulsant drugs. Both dihydropyridines increased, to similar extents, the thresholds for seizures produced by bicuculline, pentylenetetrazol, and by N-methyl-DL-aspartate. The thresholds for aminophylline were unaltered by either dihydropyridine. In contrast, the thresholds for seizures due to 4-aminopyridine in the naive animals were not changed by felodipine, but were increased by nitrendipine. The results suggest that changes in potassium, as well as calcium, may possibly be involved in some of the stages of the ethanol withdrawal syndrome.     

Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.     

Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice.

The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hrs following EtOH. Markers associated with corticosterone levels 7 hrs following EtOH and corrected corticosterone levels 6 hrs post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer

Three experiments examined the effect of either withdrawal from diazepam, or repeated treatment with the convulsant, pentylenetetrazol (PTZ), on behaviour and seizure threshold. The behaviours measured were on the elevated plus maze and in the four-plate test; seizure threshold was measured as dose of PTZ infused via the tail vein to the first clonic twitch. In experiment 1, we examined the effect of either single or repeated withdrawal from diazepam using a procedure in which the drug was administered SC in a slow release depot. Three cycles of withdrawal from diazepam were compared to a single withdrawal experience. A single withdrawal from diazepam following chronic treatment gave rise, 72 h following the last dosing, to behavioural changes, suggestive of anxiety, in both tests, but did not result in a reduced convulsant threshold. In contrast, repeated withdrawal resulted in a reduction in sensitivity in several measures of anxiety, but sensitised the mice to the convulsive effects of the PTZ. The unexpected failure to find an increased sensitivity to a convulsive agent following a single withdrawal from SC diazepam was examined in experiment 2. The seizure threshold following a single withdrawal of mice which had received diazepam chronically IP in aqueous vehicle was significantly reduced relative to vehicle-treated controls, whereas that of animals receiving the same dose SC in oil, was not. It is argued that the difference may arise from the animals treated repeatedly with IP diazepam unintentionally experiencing repeated withdrawal, since the half-life of the drug by this route is short. In experiment 3, repeated sub-convulsant PTZ treatment reduced the convulsant threshold (the dose of PTZ required to give rise to the first clonic twitch), but had no significant effect on the behavioural measures of anxiety compared to a single dose of PTZ or vehicle controls. The results suggest that repeated withdrawal from chronic treatments with diazepam sensitises mice to convulsant stimuli in a manner resembling the effects of repeated administration of sub-convulsant doses of PTZ, but that neither repeated PTZ nor repeated diazepam withdrawal results in increased sensitivity to anxiogenic stimuli; rather, repeated withdrawal from diazepam may reduce the susceptibility of mice to behavioural measures of anxiety.     

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Examined cortical EEG changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) in long-sleep (LS) and short-sleep (SS) male mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbitol, which again parallels previous behavioral data. SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS Ss; a continuous infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS Ss. The lines do not differ in rate of nicotine metabolism, hence they must differ in CNS sensitivity to nicotine. Thus, mice selectively bred for differential sensitivity to ethanol also differ in electrophysiological and behavioral responses to nicotine. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome

The effects of the anticonvulsant, gabapentin, were investigated, in mice, on the withdrawal convulsive behaviour and anxiety-related behaviour that are produced by cessation of prolonged intake of ethanol. When given at 50 or 100 mg/kg, this compound decreased the rise in handling-induced hyperexcitability which occurs during the withdrawal period; the effects were most pronounced for the first 4 hr after administration. Gabapentin also decreased the convulsive response to an audiogenic stimulus during the withdrawal period. The elevated plus-maze, with both traditional and ethological indices of activity was used as a test of anxiety-related behaviour after cessation of chronic ethanol treatment. Gabapentin, at 50 and 100 mg/kg, was found to decrease some, although not all, of the signs of withdrawal-induced anxiety. At doses up to and including 200 mg/kg, gabapentin had no effect on motor co-ordination or spontaneous locomotor activity in control animals. The results demonstrated that gabapentin has a selective action in decreasing both convulsive and anxiety-related aspects of withdrawal behaviour after chronic ethanol treatment. It is possible that further studies with this compound may shed further light on the mechanisms involved in the withdrawal syndrome.     

Locomotor activity responses to ethanol, other alcohols and GABA-A acting compounds in forward- and reverse-selected FAST and SLOW mouse lines.

Mice selectively bred for high (FAST) or low (SLOW) locomotor stimulant response to ethanol have been found to differ in response to drugs with gamma-aminobutyric acid (GABA)-ergic actions. Reverse selection produced lines that are similar in sensitivity to ethanol stimulation (r-FAST and r-SLOW) and provided a unique model for testing hypotheses about shared genetic influence on sensitivity to ethanol and GABAergic drugs. FAST mice were more stimulated than SLOW mice by all drugs tested: ethanol, methanol, n-propanol, t-butanol, pentobarbital, diazepam, and allopregnanolone. In contrast, r-FAST and r-SLOW mice differed in sensitivity to only a few isolated drug doses. Locomotor responses of each reverse-selected line were significantly different from the responses of their respective forward-selected line for all drugs. Results support an effect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of physical dependence on diazepam by ondansetron in rats

The effects of ondansetron, a 5-HT3 antagonist, on the development of physical dependence on diazepam were examined in rats using a drug-admixed food method. Rats were treated with diazepam or diazepam in combination with ondansetron for 26 days. After an abrupt withdrawal from diazepam, the incidence of withdrawal signs, such as jerks, tremors and convulsions, and withdrawal scores, were potentiated by co-administration of ondansetron. On the other hand, rats which had been treated with ondansetron alone for 33 days did not show any withdrawal signs after abrupt withdrawal from ondansetron. These findings suggest that ondansetron does not possess physical dependence liability, but does potentiate the development of physical dependence on diazepam. Regulation of serotonergic neurons through 5-HT3 receptors may affect the development of physical dependence on diazepam.     

Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice

Individually housed DBA/2J mice were fed a liquid diet in which ethanol supplied 33% of the calories. The level of physical dependence that developed was estimated by scoring convulsions, elicited by handling the mice, after discontinuing the alcohol diet. The severity of the withdrawal reaction increased progressively with duration (5-12 days) of alcohol administration. A 2-day period on the diet produced no withdrawal reaction. Pretreatment of the mice with alcohol in their drinking water slightly increased the subsequent intake of the liquid diet. "Effective" alcohol intake was defined as uninterrupted alcohol consumption above 10 g/kg/day. Withdrawal scores correlated better with effective intake than with total intake under a variety of conditions. We interpret this to mean that brief interruptions in drinking (1 day) may allow the accrued physical dependence to disappear. On the basis of their effective alcohol intake, mice could be assigned to nondependent, moderately dependent or severely dependent groups for further study of the nature of physical dependence.     

Anxiogenic-like effect of chronic corticosterone in the light-dark emergence task in mice.

[Correction Notice: An erratum for this article was reported in Vol 120(6) of Behavioral Neuroscience (see record 2006-22387-011). In the article "Anxiogenic-Like Effect of Chronic Corticosterone in the Light-Dark Emergence Task in Mice," by Paul Ardayfio and Kwang-Soo Kim (Behaviorial Neuroscience, 2006, Vol. 120, No. 2, pp. 249-256), the measurement unit of the corticosterone concentration on p. 250 (under the Drugs heading) was incorrect. The correct unit is μg/ml. The corrected sentence follows: "Corticosterone (Sigma, St. Louis, MO) was dissolved in ethanol, diluted, and administered via the drinking water at a final concentration of 0 or 35 μg/ml in 0.3% ethanol."] Chronic hypercortisolemia is a hallmark of neuroendocrine and psychiatric disorders, such as Cushing's disease and depression. Whether cortisol directly contributes to the altered mood and anxiety symptoms seen in these diseases remains unclear. To address this, the authors have modeled hypercortisolemia by administering corticosterone in the drinking water of female Swiss Webster mice for 17 or 18 days (13 mg/kg). Light-dark emergence, startle habituation, and startle reactivity were measured. Chronic but not acute treatment with corticosterone increased the latency to emerge into the light compartment, an anxiogenic-like effect. Chronic corticosterone treatment did not affect startle habituation, but did reduce startle reactivity. This study suggests that chronic hypercortisolemia may contribute to anxiety-related behavior in patients with Cushing's disease and depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of hypnotics on mice genetically selected for sensitivity to ethanol

It was previously shown that the rate of disappearance of blood ethanol was identical for two lines of mice selectively bred for differences in sleep-time after ethanol administration. The ED50 values for the loss of righting response with ethanol were significantly different at 3.64 g per kg for the SS line and 1.65 g per kg for the LS line. In the present study the mean sleep time is 367 sec for SS mice and 9342 sec for LS mice. The ED50 values remain essentially the same as previously reported. Unchanged LD50 values for ethanol, however, are not different at 4.8 g per kg for the SS and 4.5 g per kg for the LS line of mice. The ED50 value for loss for righting response following administration of methanol, butanol and t-butanol is approximately 2 fold greater for the SS line of mice than for the LS line. The ED50 values for sodium pentobarbital or ether in the 2 lines of mice for loss of righting response are virtually identical. In addition, the sleep-time values obtained after the administration of pentobarbital, chloral hydrate, trichloroethanol and paraldehyde are not significantly different. These data indicate that while the SS and LS lines of mice differ in central nervous system sensitivity to ethanol, methanol, butanol and t-butanol it is implied that they do no differ in central nervous system sensitivity to other hypnotic agents tested. Proof of this latter suggestion awaits determination of metabolic rates, and brain levels of these other depressants.     

A study of the relationship between home care services and hospital readmission of patients with congestive heart failure

Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.