乙醇对嗜酒和非嗜酒小鼠体重和肝脏组织形态的影响

目的比较乙醇对嗜酒和非嗜酒小鼠躯体损害的易感性。方法以近交系C57BL/6J小鼠(嗜酒者)和远交系ICR小鼠(非嗜酒者)为实验动物,采用强制性饮酒程序:饮酒组小鼠饮用乙醇溶液8d,乙醇浓度从3%递增至20%。每天检测小鼠体重、摄食量、饮液量和乙醇摄入量。饮用乙醇期间取小鼠肝脏用组织化学方法观察肝脏组织病理学变化。结果乙醇对嗜酒小鼠体重增长的抑制作用明显强于非嗜酒小鼠。乙醇对两组小鼠的摄食量均有抑制作用,抑制程度无显著差异。乙醇抑制非嗜酒小鼠的饮液量,但对嗜酒小鼠无影响。实验期间两组小鼠的饮酒量相当,但嗜酒小鼠的肝脏损伤更为严重。结论嗜酒小鼠对乙醇毒性作用的耐受性弱于非嗜酒小鼠。     

Oxidation of alcohol in free-moving mice from high and low preference strains

Free-moving mice from the high-alcohol preference C57BL/6J strain and low-preference DBA/2J strain were slowly fed [2-14C]ethanol intragastrically until anesthesia was achieved. Behavior was monitored in a Plexiglas metabolic chamber while 14CO2 was simultaneously trapped to determine the rate of ethanol metabolism. Average time to the loss of the righting reflex in the DBA/2J was 21.9 min and 27.9 min for the C57BL/6J strain (p less than 0.005). Elimination of 14CO2 was slightly higher (n.s.) in the DBA/2J strain for the entire monitoring period. Infusion of ethanol via the tail vein yielded identical results indicating that the slower elimination rate in the C57BL/6J strain could not be the result of slower absorption across the gut wall. Infusion via the tail vein with radioactive sodium bicarbonate indicated that the DBA/2J strain has a higher rate of CO2 expiration (n.s.). Consequently, the higher rate of 14CO2 expiration from ethanol oxidation may not reflect a higher rate of metabolism. These results are discussed in terms of the apparent differences between these strains in neural sensitivity to ethanol.     

Effects of abused inhalants and GABA-positive modulators in dizocilpine discriminating inbred mice

There is in vitro evidence that some of the effects of abused volatile solvents may be produced by actions at the NMDA receptor. In addition, some solvents produce phencyclidine-like discriminative stimulus effects. The major goal of the present study was to further compare abused solvents to NMDA antagonists by testing them in two strains of mice trained to discriminate 0.17 mg/kg of the very selective uncompetitive NMDA antagonist, dizocilpine, from saline and contrast those results with several GABA(A)-positive modulators, PCP and ethanol. The results indicated that the discriminative stimulus produced by 0.17 mg/kg dizocilpine was highly specific in both mouse strains. PCP produced 91% dizocilpine-lever responding in C57BL/6J mice, but only 56% dizocilpine-lever responding in DBA/2J mice. Pentobarbital, midazolam and ethanol produced at least some overlap in discriminative stimulus effects with dizocilpine in one or both mouse strains. In contrast, toluene, 1,1,1-trichloroethane (TCE), xylene and methoxyflurane produced saline-appropriate responding almost exclusively. These data indicate that, at least under the specific conditions tested, abused volatile solvents do not have substantial dizocilpine-like discriminative stimulus effects in either C57BL/6J or DBA/2J mice, providing little support that NMDA antagonism plays a central role in the production of this abuse-related effect.     

Consumption of intoxicating beverages by rats and mice exhibiting high and low preferences for ethanol

Lines of rats selectively bred for alcohol consumption or avoidance (AA and ANA, ALKO, Finland) as well as inbred strains of mice (C57/BL/6J and DBA/2J) and common female Wistar rats (Charles River) exhibiting high and low preferences for ethanol were tested under free-choice conditions for their consumption of solutions of ethanol (5, 10, or 15 g/100 ml tap water), sodium pentobarbital (0.19, 0.038, 0.076 g/100 ml tap water), and different beverages containing ethanol in the range of 8.1–9.6% (red and white wine, Scotch, ethanol in Hawaiian Punch). The Wistar rats and the mice classified as alcohol-preferring also tended to consume more of the pentobarbital solution than did alcohol-avoiding animals. Alcohol-nonaccepting (ANA) rats, however, consumed considerably more of all three pentobarbital solutions than did the alcohol-accepting (AA) rats. The intake of pentobarbital by the ANA rats and C57/BL/6J mice was in the range of 25–40 mg/kg/day, quantities that might be expected to produce pharmacological effects discriminable by those animals. The intake of ethanol by ANA rats was markedly elevated when the ethanol was contained in white wine or in punch.     

Genetic differences in the rewarding and activating effects of morphine and ethanol

The influence of genotype on the rewarding and locomotor activating effects of morphine and ethanol was examined in the place conditioning paradigm. Two inbred mouse strains (C57BL/6J and DBA/2J) were exposed to a differential conditioning procedure in which each mouse received four pairings of a distinctive floor stimulus with IP injection of morphine (0, 2.5, 5 or 10 mg/kg) or ethanol (0, 1, 2, 3 or 4 g/kg). A different floor stimulus was paired with saline. Conditioning trials lasted 30 min and each experiment concluded with a floor preference test in the absence of drug. In accord with previous studies, morphine evoked a dose-dependent increase in activity during conditioning that was greater in C57BL/6J mice than in DBA/2J mice. In contrast, ethanol produced a dose-dependent increase in activity that was greater in DBA/2J than in C57BL/6J mice. Both strains showed conditioned place preference with morphine, but only the DBA/2J strain showed conditioned place preference with ethanol. No conditioned place aversion was seen. With both drugs, stronger place preference conditioning was obtained in DBA/2J mice, supporting the general conclusion that sensitivity to drug reward is influenced by genotype. The fact that the same genotype is more sensitive to the rewarding effects of two different drugs supports theories postulating commonality in the biological mechanisms of drug reward. Although the outcome of the ethanol study supports predictions of the psychomotor stimulant theory of addiction concerning the relationship between drug-induced activation and reward, the outcome of the morphine study does not. The direction of the strain difference in conditioned place preference is opposite to what might be predicted on the basis of strain differences previously reported in drug consumption and preference studies, suggesting that genetic differences in drug consumption may not accurately reflect postabsorptive motivational effects of drug.     

Distribution and excretion of 2,3,7,8-tetrachlorodibenzofuran in C57BL/6J and DBA/2J mice

The distribution and excretion of the toxic pollutant, 2,3,7,8-tetrachlorodibenzofuran (TCDF), was studied in male C57BL/6J and DBA/2J mice (22–29 g). [¹⁴C]TCDF was administered iv at a dose of 0.1 μmmol/kg. The liver was the major site of TCDF accumulation, with more TCDF in the livers of C57BL/6J mice compared to DBA/2J mice. TCDF had a half-life of approximately 1.8 days in the livers of both strains. At 7 hr and 1 day, respectively, radioactivity was redistributed to adipose tissue of C57BL/6J mice and DBA/2J mice. The terminal $\text{T}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of TCDF in adipose tissue of C57BL/6J mice was 1.1 days, whereas it was 6.8 days in DBA/2J mice; the sixfold longer half-life in DBA/2J mice may be related to the approximately 36% greater adipose tissue content of this strain which may sequester more TCDF. More than 80 and 55% of the dose was excreted in the feces of C57BL/6J and DBA/2J mice, respectively, within 10 days as polar metabolites. The whole body half-life of TCDF was 2 days in C57BL/6J and 4 days in DBA/2J mice. Thus, DBA/2J mice sequester more of the TCDF dose in adipose tissue, accounting for a relatively slower rate of clearance and lower concentrations of TCDF at the putative target site(s) for toxic action.     

Ethanol intoxication as function of genotype dependent responses in three inbred mice strains

Three strains of mice, ICR Swiss, DBA/2J and C57B1/6J were compared for initial sensitivity, recovery from intoxication, and acute tolerance development to ethanol. The C57B1/6J mice were found to be less sensitive and to recover more rapidly from the effects of the same dose of ethanol than the other two strains treated. None of the strains tested demonstrated acute tolerance to ethanol when given the same dose 3 hours later.     

Characteristics of effects of repeated scopolamine administration on ambulatory activity in mice and methamphetamine sensitivity in the scopolamine-experienced mice: comparison among 6 strains

Effects of scopolamine (0.5 mg/kg, s.c.) on ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB, C57BL, C3H and DBA). Scopolamine increased ambulatory activity, and the sensitivities were in the order of ICR greater than C3H greater than BALB greater than DBA greater than C57BL greater than dd. This was different from that produced by methamphetamine (2 mg/kg, s.c.) where the order was ICR greater than dd greater than DBA greater than C3H greater than C57BL greater than BALB. A tolerance to the ambulation-increasing effect of scopolamine was progressively produced in dd, ICR, C57BL and DBA strains, but not in BALB and C3H strains, when the drug was administered 5 times at intervals of 3-4 days. The repeated scopolamine treatment elicited a major enhancement of the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) in BALB and C3H strains and a minor enhancement in the C57BL strain, whereas dd, ICR and DBA strains did not exhibit a marked change in the sensitivity to methamphetamine even after the same treatment with scopolamine. These results suggest that the ambulation-increasing effect of scopolamine is different from that of methamphetamine and that the interaction between scopolamine and methamphetamine varies among different strains of mice.     

Cocaine produces low dose locomotor depressant effects in mice

Cocaine produces several behavioral effects, most notably locomotor stimulation. Biochemically, cocaine is known to inhibit reuptake at the three monoamine transporter sites, and may have highest affinity at the serotonin transporter. Serotonin augmentation has been associated with decreases in behavioral activity, but cocaine has not been reported to produce behavioral depressant effects except at high doses which cause stereotypy and disruption of behavior. This study examined the effects of relatively low doses of cocaine, in the range of 0.1–10 mg/kg, on locomotor activity in C57BL/6J and DBA/2J mice. A biphasic dose-response curve was seen for both strains. At the lowest doses, activity was depressed. As the dose of cocaine increased, activity returned to baseline, and at the highest doses, increases in locomotor activity were found. DBA/2J mice were depressed at a lower dose of cocaine than were C57BL/6J mice; however, C57BL/6J mice showed locomotor depression over a broader range of doses. Activity was maximally depressed at 0.1 mg/kg for DBA/2J mice, and maximally depressed at 0.3 mg/kg for C57BL/6J mice. Thus, low doses of cocaine are shown to produce significant decreases in locomotor activity in two strains of mice. It is postulated that these low doses of cocaine which depress locomotor activity do so via inhibition of serotonin uptake, resulting in potentiation of serotonergic activity.     

Inherent differences in sensitivity to methylxanthines among inbred mice

The behavioral effects of caffeine, theophylline, paraxanthine, and theobromine on locomotor activity were analyzed in four strains of inbred mice that were previously shown to differ in their acute toxic responses to caffeine administered at high dosages. Dose response curves for the effects of caffeine, theophylline, paraxanthine and theobromine on locomotor activity were established in CBA/J, C57BL/6J, DBA/2J and SWR/J strains of inbred mice. Paraxanthine was the maximally effective methylxanthine in the CBA/J, DBA/2J and SWR/J strains, while in the C57BL/6J strain, caffeine was the maximally effective methylxanthine. Theophylline failed to stimulate locomotor activity in the C57BL/6J strain and theobromine failed to stimulate activity in all of the strains tested. Decreases in locomotor activity were seen at the 100 mg/kg dose of caffeine in the C57BL/6J mice and at the 100 mg/kg dose of theophylline in the C57BL/6J, DBA/2J and SWR/J strains. Theobromine produced decreases in locomotor activity in the C57BL/6J, DBA/2J and SWR/J strains of mice. In contrast to the other methylxanthines, paraxanthine failed to decrease activity across the range of doses tested (1.0-150 mg/kg). These data suggest that the methylxanthines have genetically specified multiple modes of action upon locomotor activity and that the use of genetically distinct strains of mice may have important value in the neurochemical and pharmacological dissection of methylxanthine-induced behavioral effects.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced change in intestinal function and pathology: evidence for the involvement of arylhydrocarbon receptor-mediated alteration of glucose transportation

Although numerous studies have been performed to clarify the mechanism(s) underlying the toxicological responses induced by dioxins, their effect on the intestine is less well understood. To address this issue, we examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the pathology and function of the intestine in arylhydrocarbon receptor (AhR)-sensitive (C57BL/6J) and -less-sensitive (DBA/2J) mice. A single oral administration of TCDD (100 mug/kg) to C57BL/6J mice produced changes in villous structure and nuclear/cytoplasm ratio in the epithelial cells of the intestine. Furthermore, in an oral glucose tolerance test, the serum glucose level was significantly increased in the C57BL/6J mouse but not in the DBA/2J mouse by TCDD treatment. In agreement with this, the expression of intestinal mRNAs coding sodium-glucose co-transporter 1 (SGLT1) and glucose transporter type 2 were increased only in C57BL/6J mice by TCDD. The increase in the former transporter was also confirmed from its protein level. The glucose level in the intestinal contents is thought to be one of the factors contributing to SGLT1 induction. Concerning with this, the intestinal activity of sucrase and lactase was significantly increased only in C57BL/6J mice by TCDD. These results suggest that while TCDD produces initial damage to the intestinal epithelium, the tissues induce SGLT1 to facilitate the absorption of glucose, which is expected, at least partially, to combat the wasting syndrome induced by TCDD. The data provided here also suggest that AhR is involved in the mechanism of SGLT1 induction.     

Using pentobarbital to assess the sensitivity and independence of response-bout parameters in two mouse strains

A recently developed model posits that a bout of operant responding comprises three different components: bout initiation rate, within-bout response rate and bout length. Each parameter is thought to be affected by different classes of variables. Pentobarbital was used to assess the independence and sensitivity of these parameters in two mouse strains, BALB/c and C57BL/6, selected because of their different behavioral characteristics. With or without a running wheel present, BALB/c and C57BL/6 mice nose-poked under a Percentile 10:0.5 schedule designed to select high response rates while holding reinforcement rate constant. Baseline rates of nose-poking were higher for BALB/c mice than for C57BL/6 mice, but no strain difference occurred in baseline distance run. Nose-poking occurred at a higher rate when the wheel was absent from the chamber for both strains, and this was due to longer bout lengths and higher bout initiation rates. Nose-poke rates were increased by the 5.6-17 mg/kg doses of pentobarbital, especially in C57BL/6 mice. Pentobarbital only decreased running. No strain differences in pentobarbital sensitivity were observed for running. Whether reinforcement was extrinsic or intrinsic to the response was hypothesized to influence pentobarbital's effects. The different bout parameters helped dissect pentobarbital's effects and were selectively affected by pentobarbital.     

Enhanced acquisition of cocaine self-administration by increasing percentages of C57BL/6J genes in mice with a nonpreferring outbred background

Rationale Individual differences in the propensity to acquire drug self-administration may have a substantial genetic basis.Objectives To study the genetic contribution to cocaine self-administration by comparing hybrids of cocaine preferring (C57BL/6J) and nonpreferring (ICR) mice.Methods ICR and C57BL/6J parental strains were compared to hybrids with 75% ICR:25% C57BL/6J, 50% ICR:50% C57BL/6J, and 25% ICR:75% C57BL/6J genetic backgrounds for acquisition of sucrose pellet and intravenous cocaine self-administration in 1-h test sessions. Mice that acquired cocaine self-administration were subsequently tested in a between-session self-administration dose-response procedure.Results Increasing presence of C57BL/6J genes increased the percentage of mice that acquired sucrose pellet self-administration in the first test session. In lever-trained mice, only 19% of ICR mice met acquisition criteria for cocaine self-administration after 15 sessions, whereas 76% of C57BL/6J mice met acquisition criteria, although both strains initially sampled a similar number of cocaine injections. Increasing the percentage of C57BL/6J genes in the nonpreferring ICR background to 50 and 75% led to increasing percentages of mice that met acquisition criteria to 31 and 52%, respectively. In mice that acquired self-administration, only mice with 75% C57BL/6J genes showed a typical inverted U-shaped self-administration dose–response curve, whereas the curve was flat across doses for mice with ≤50 and 100% C57BL/6J genes.Conclusions The findings are consistent with a genetically based dose-dependent enhancement of cocaine reinforcement by C57BL/6J genes. These results suggest that heritable traits impart a substantial genetic load that facilitates the propensity for cocaine addiction among individuals in outbred populations.     

Effects of E-2078, a stable dynorphin A(1–8) analog, on sedation and serum prolactin levels in rhesus monkeys

Rationale: In previous comparisons with C57BL/6J mice, DBA/2J mice have been characterized as ”hyporesponsive” to cocaine’s rewarding effect in the conditioned place-preference paradigm. This finding contrasts with other studies showing greater sensitivity of DBA/2J mice to the rewarding effects of ethanol and morphine in the place conditioning task. Objectives: The purpose of the present study was to examine cocaine- induced place conditioning in both strains using apparatus and procedures similar to those used previously to assess ethanol and morphine preference conditioning. Methods: Mice from both strains were exposed to an unbiased place-conditioning procedure using 1, 10, or 30 mg/kg cocaine. Conditioning trial duration was 15, 30, or 60 min. Results: In general, C57BL/6J mice displayed a significant conditioned place preference that was relatively unaffected by cocaine dose or trial duration. In contrast, DBA/2J mice showed no place conditioning at the shortest trial duration, but an increasing level of preference as trial duration increased. At the longest trial duration, both strains showed similar levels of place preference. Conclusions: Genetic differences in sensitivity to cocaine’s rewarding effect depend critically on temporal parameters of the place-conditioning procedure. One possible interpretation of these findings is that short trial durations produce conditioned activity responses that interfere more with expression of conditioned place preference in DBA/2J mice than in C57BL/6J mice. More generally, these findings underscore the need for caution when drawing conclusions about genetic differences in place conditioning, especially when using this paradigm to evaluate the effects of gene knockouts or insertions on drug reward. Received: 31 December 1998 / Final version: 15 April 1999     

Differential effects of scopolamine and D-amphetamine on avoidance: Strain interactions.

In a discriminated Y-maze avoidance task it was observed that mice of the A/J strain were superior to mice of the DBA/2J strain, which in turn made more avoidance responses than C57BL/6J mice. Moreover, the A strain was also observed to acquire a discrimination problem more readily than either of the other strains. Administration of scopolamine enhanced active avoidance performance in A, but not DBA/2 or C57BL/6 mice. D-Amphetamine improved performance in both A and DBA/2 mice but had negligible effects on the performance of the C57BL/6 strain. Neither drug affected discrimination performance irrespective of strain. In an inhibitory avoidance task the C57BL/6 strain was found to perform more poorly than the A strain which was inferior to DBA/2 mice. Scopolamine disrupted performance in all three strains, while d-amphetamine was found to disrupt the performance of the A and DBA/2 strains only. The results were interpreted in terms of the role of associative and nonassociative effects of shock in modulating avoidance behavior.     

Distribution, excretion, and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J, DBA/2J, and B6D2F1/J mice

The strains of mice, C57BL/6J, DBA/2J, and B6D2F1/J, have been used as models to study the mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The distribution, excretion, and metabolism of this compound was studied in male C57BL/6J, DBA/2J, and B6D2F1/J mice following the intraperitoneal administration of radiolabeled TCDD at a dose of 10 micrograms/kg. In all strains, the liver and adipose tissue were the major sites for the accumulation of 3H-TCDD, with more 3H-TCDD being distributed to the livers of the C57BL/6J and B6D2F1/J strains as compared to the DBA/2J strain. While in all strains the feces were the major route of elimination, the total amount of 3H-TCDD-derived radioactivity excreted in the feces amounted to approximately 72% of the original dose in the C57BL/6J and B6D2F1/J strains whereas this was only 54% in the DBA/2J strain. The half-lives for the cumulative excretion of radioactivity in the feces were similar in all strains. The half-life for the excretion of radioactivity in the urine was considerably greater in the DBA/2J strain as compared to the C57BL/6J and B6D2F1/J strains. The estimated half-lives for the total cumulative excretion of 3H-TCDD-derived radioactivity by all routes was 11.0, 24.4, and 12.6 days for the C57BL/6J, DBA/2J, and B6D2F1/J strains, respectively. Greater than 85% of the total radioactivity excreted in urine, bile, and feces from all three mouse strains was present as metabolites of TCDD.     

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists

Rationale Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. Objectives The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. Methods The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Results Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-β-erythroidine (DHβE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Conclusion Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.     

Relationship between the murine Ah phenotype and the hepatic uptake and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin

The influence of the Ah locus on the hepatic uptake and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied using isolated hepatocytes from Ah responsive C57BL/6J (C57) and nonresponsive DBA/2J (DBA) mice. Hepatocytes from control and TCDD-pretreated C57 and DBA mice were incubated with purified [14C] TCDD (2.2 microM) for 8 hr in the metabolism studies or 2 hr in the uptake studies. Mice were pretreated 7 days prior to hepatocyte isolation with TCDD at doses that maximally induce aryl hydrocarbon hydroxylase activity (C57: 3 micrograms/kg, ip; DBA: 30 micrograms/kg, ip) or at doses approaching the LD50 value (C57: 150 micrograms/kg, ip; DBA: 600 micrograms/kg, ip). Hepatocytes isolated from untreated C57 and DBA mice had similar uptake of [14C]TCDD, and, at all doses, TCDD pretreatment increased [14C]TCDD uptake. The rates of hepatic TCDD metabolism over the first 2 hr of incubation were similar for control C57 and DBA mice, although some qualitative differences in metabolites were detected by HPLC. TCDD pretreatment at doses of 3 and 30 micrograms/kg for C57 and DBA mice, respectively, produced no detectable quantitative or qualitative changes in TCDD metabolism, despite increases in cytochrome P-450 content, 7-ethoxyresorufin O-deethylase (EROD) activity, and benzo[a]pyrene (BaP) metabolism. Pretreatment of C57 and DBA mice with the respective LD50 doses of TCDD decreased the rate of TCDD metabolism by hepatocytes, although cytochrome P-450 content, EROD activity, and BaP metabolism were increased. These results suggest that the uptake and the rate of hepatic metabolism of TCDD do not correlate with genetic differences at the murine Ah locus.     

Taurine and ethanol interactions: behavioral effects in mice

Taurine is an abundant amino acid in the brain that shares pharmacological effects and similar potency with ethanol. Recently, taurine-containing beverages have been reported to enhance the euphoric effects of ethanol, though the extent of this effect and the role of taurine remain speculative. The present study was designed to explore interactions between taurine and ethanol on several behaviors including locomotion, ataxia, and loss of righting. Two strains of mice, C57BL/6J and DBA/2J mice, were used to examine potential strain differences. In the first experiment, effects of various doses of taurine (0.3-3.0 g/kg), ethanol (1.0-4.2 g/kg), or taurine in combination with ethanol were assessed in a within-subjects design. Although taurine did not appear to alter effects of ethanol on any measure in either strain, the development of tolerance to locomotor effects and sensitization to ataxic effects of ethanol in DBA/2J mice complicated interpretation of these results. In a second experiment, drug-na?ve mice were assigned to one of four treatment groups: saline+saline, saline+ethanol (1.78 g/kg), taurine (1.78 g/kg)+saline, or ethanol+taurine. In this experiment, taurine pretreatment significantly attenuated the locomotor-stimulating effect of ethanol in both strains (but to a greater extent in C57BL/6J mice) and appeared to reduce the ataxic effects of ethanol in C57BL/6J mice. In conclusion, the interaction between taurine and ethanol is subtle. Further, results are inconsistent with the notion that taurine plays a major role in the locomotor, ataxic, or loss of righting effects of ethanol.     

Brain acetaldehyde after ethanol administration

Gas Chromatographic determination of blood and brain levels of acetaldehyde was made by two methods in C57B1/6J and DBA/2J mice after a single injection of ethanol (3 g/kg, i.p.). Ninety min after the administration of ethanol, blood levels of acetaldehyde were 70 nmoles/ml and 200 nmoles/ml for the C57 and DBA mice respectively. Corresponding brain levels, after correcting for blood content, were 6.4 nmoles/g and 17.3 nmoles/g for C57 and DBA mice respectively. These results indicate that blood acetaldehyde levels after acute administration of ethanol do not reflect those found in brain. The results further suggest that brain may be protected, at least in part, from concentrations of acetaldehyde found in blood, by an effective metabolic barrier.