Seizure sensitivity and GABAergic modulation of ethanol sensitivity in selectively bred FAST and SLOW mouse lines

FAST and SLOW selected mouse lines were bred for differences in locomotor response to low-dose ethanol. FAST mice exhibit an extreme stimulant response and SLOW mice exhibit locomotor depression at the same ethanol dose. We tested the hypothesis that gamma-aminobutyric acid (GABA) systems modulate ethanol's stimulant effects by examining convulsant responses to GABAA receptor ligands, and by assessing the effects of GABAA and GABAB ligands on locomotor activity in the presence and absence of EtOH. FAST mice were more sensitive to the convulsant effects of GABAA drugs, and to one of two non-GABAergic drugs also tested. FAST and SLOW mice differed in locomotor responses to two benzodiazepines, but not to other GABAA receptor ligands. Ethanol's stimulant effects were not selectively altered by bicuculline or picrotoxin. The selected lines differed in sensitivity to the locomotor depressant effects of the GABAB agonist, baclofen. Ethanol-stimulated activity of FAST mice was inhibited by baclofen, and this effect was reversed by administration of the GABAB antagonist, CGP-35348. These GABAB receptor mediated effects were replicated in DBA/2J inbred mice that exhibit extreme sensitivity to ethanol's stimulant effects. In summary, we found moderate to strong evidence that some sites on the GABAA receptor complex were altered as a consequence of selection of FAST and SLOW mice, but found little support for GABAA mediation of EtOH-stimulated activity. In contrast, we found moderate evidence for differential alteration of GABAB receptor function; however, GABAB receptor involvement in ethanol-stimulated activity was strongly supported by results in the selected lines and an inbred strain.     

Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes.

Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitivity to ethanol-induced ataxia in HOT and COLD selected lines of mice

Studies with inbred strains of mice have suggested that there may be a genetic correlation between strain sensitivities to the ataxic and hypothermic responses to ethanol (EtOH), which would suggest that some genes influence both responses. To test this hypothesis, EtOH sensitivity was determined in replicate lines of mice selectively bred for sensitivity (COLD) or resistance (HOT) to acute ethanol hypothermia. Several tests were used to index ataxia, related traits such as muscle strength, and locomotor activity. The screen test yielded a dose-dependent EtOH-induced decrease in performance that did not differ between the selected lines. Based on the dose-response characteristics of this task, 2.5 g/kg of EtOH was used as the test dose for the remaining experiments. Results from the fixed-speed rotarod and the grid test of motor incoordination also indicated no significant differences between HOT and COLD mice in sensitivity to EtOH impairment. When the selected lines were tested on an accelerating rotarod, COLD mice were impaired by the acute EtOH injection, but HOT mice were unaffected. COLD mice were more sensitive to EtOH-induced decrements in grip strength and locomotor activity. Overall, the results indicated that HOT and COLD mice were only differentially sensitive to EtOH in some tasks related to ataxia, suggesting that some genes must be associated uniquely with EtOH-induced hypothermia or ataxia. The mixed results from the various tests indicate that ataxia can best be conceived as a group of related complex behaviors that cannot be assessed adequately by the use of a single task and that ataxia-related behaviors are influenced by different groups of genes.     

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)     

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)     

Differential effects of GABA(A) and GABA(B) agonists on sensitization to the locomotor stimulant effects of ethanol in DBA/2 J mice

Contemporary theories of drug abuse suggest that behavioral sensitization plays an important role in addiction. However, few studies have examined the mechanisms underlying behavioral sensitization to ethanol. The present study examined the ability of THIP (2, 4, or 8 mg/kg) and baclofen (5.0, 6.25, or 7.5 mg/kg), GABA(A) and GABA(B) agonists, respectively, to prevent development of sensitization to the locomotor stimulant effects of ethanol (2 g/kg) in DBA/2 J mice. Ethanol was administered immediately before four 5-min activity trials conducted at 48-h intervals. Administration of ethanol on each of the four trials resulted in behavioral sensitization in control groups. While having few effects on activity when given alone, both GABA agonists completely blocked the acute stimulant response to ethanol on the first trial. Administration of THIP prior to ethanol on each trial failed to prevent development of sensitization. In contrast, all doses of baclofen blocked sensitization. Assessment of blood ethanol levels 15, 50 and 100 min after administration of ethanol indicated that baclofen did not change the pharmacokinetics of ethanol. These results indicate an important role for GABA(B) receptors, but not GABA(A) receptors, in development of sensitization to the locomotor stimulant effects of ethanol.     

Ethanol effect on activation and maintenance of cold stress response in immature rats

Rats at thermoneutral ambient temperature (Ta) exhibit change in thermoregulatory response to ethanol (EtOH) from 2 to 15 days of age. In the present study, rats at 2-3, 8-9, and 14-15 days of age were administered either saline or EtOH (4 g/kg b.wt.;IP) using two different routines to determine EtOH effect on specific cold defense mechanisms. Injection of EtOH in the first routine occurred after exposure to cold Ta, to determine effect on maintenance of cold thermogenesis. EtOH-induced metabolic depression increased from 3 to 8 days of age, with little change after this time. Injection of EtOH in the second routine was at thermoneutral Ta, followed at 20 min postinjection by rapid exposure to cold Ta to determine effect on activation of cold thermogenesis. EtOH-treatment delayed onset of cold thermogenesis at 2-3 and 14-15 days of age, and completely eliminated 8-9-day-old response to cold Ta. Rats exposed to cold Ta at 2-3 days of age exhibited a slower rate of EtOH absorption and lower blood EtOH concentration than rats in the older groups, to explain some age differences in EtOH response.     

Bivalent effects of MK-801 on ethanol-induced sensitization do not parallel its effects on ethanol-induced tolerance.

The relationship between the effects of the N-methyl-D-aspartate (NMDA) antagonist MK-801 on acute responses to ethanol and its ability to block ethanol sensitization and tolerance was examined in DBA/2J mice. Cross-sensitization between these drugs was also studied. Repeated administration of 0.1 mg/kg MK-801 with ethanol potentiated, whereas 0.25 mg/kg attenuated, sensitization to ethanol's locomotor stimulant effects; rearing was similarly affected. There was evidence for cross-sensitization between ethanol and 0.25 mg/kg MK-801. MK-801 potentiated ethanol's ataxic effects in the grid test, but had no effect on tolerance to this effect. MK-801's effects on ethanol sensitization appeared to be related to its own behavioral effects, rather than NMDA receptor blockade per se. Further, these studies demonstrate dissociation between ethanol sensitization and tolerance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of ethanol in adolescent and adult rats

Alcohol use in children and adolescents is widespread. However, very little is known about the effects of alcohol exposure during this period of postnatal development. The goal of the present study was to compare the relative sensitivity to the sedative effects of alcohol in periadolescent and adult rats. After treatment with either 4 or 5 g/kg ethanol, both 20- and 30-day-old rats regained their righting reflex significantly earlier than 60-day old rats. In 30-day-old rats, serum ethanol concentrations (SECs) were significantly greater at the time of the recovery of the righting reflex than 60-day-old rats. Developmental differences in the effects of ethanol on locomotor activity were also observed. In 60-day-old rats, 2.5 g/kg ethanol generally decreased locomotor activity. Ethanol did not significantly alter locomotor activity in 20- and 30-day-old rats. Finally there were significant developmental differences in the pharmacokinetics of ethanol with a significant delay in the time to peak SECs in 60-day-old rats relative to 20- and 30-day-old rats. These findings indicate that peri-adolescent rats are less sensitive to the sedative effects of ethanol as they recovered their righting reflex earlier and at significantly higher SECs than adult rats.     

Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol.

This study examined the effect of repeated ethanol (EtOH) injections that induced behavioral sensitization on subsequent acquisition of EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA). CTA acquisition was assessed in independent groups of EtOH-sensitized and nonsensitized genetically heterogeneous female mice after injections of saline; 1, 2, or 4 g/kg EtOH; or 2 or 4 mEq/kg LiCl. Saline and 1 g/kg EtOH did not induce CTA. Four g/kg EtOH and 4 mEq/kg LiCl induced similar levels of CTA in EtOH-sensitized and nonsensitized groups. CTA induced by 2 g/kg EtOH and 2 mEq/kg LiCl was attenuated in EtOH-sensitized mice compared with nonsensitized counterparts. Thus, a sensitizing regimen of EtOH preexposure resulted in both a decrease in EtOH and LiCl aversion and an increase in EtOH locomotor sensitivity; such changes could ultimately contribute to enhanced EtOH intake and potentially to EtOH abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone and baclofen attenuate ethanol's locomotor-activating effects in preweanling Sprague-Dawley rats.

Heterogeneous rat strains appear to be particularly sensitive to the sedative effects of ethanol as adults and insensitive to ethanol's stimulant effects. Recently, the authors found that ethanol induces stimulant effects in preweanling Sprague-Dawley rats. In adult mice, these effects seem to be governed by the mesocorticolimbic dopaminergic pathway, which can be modulated by means of GABA B agonist (baclofen) or opioid antagonist (naloxone) treatments. This study tested whether these pharmacological treatments might reduce the activating effect of ethanol in preweanling Sprague-Dawley rats. Twelve-day-old pups given naloxone (Experiment 1A) or baclofen (Experiment 1B) before ethanol administration were tested in terms of locomotor activity in a novel environment. Naloxone and baclofen significantly reduced the stimulating effect of ethanol but had no effect on locomotor activity patterns in water-treated controls. Blood ethanol levels were not affected by naloxone or baclofen (Experiment 2). During the preweanling period, opioid and GABA B receptors seem to be involved in the stimulating effect of ethanol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Natural killer cells: endothelial interactions, migration, and target cell recognition

Our previous studies with mice showed that chronic ethanol (EtOH) administration affected the incorporation of unsaturated free fatty acids (FFA) into four major brain phospholipids (PL). In the current study, we investigated the effects of ganglioside GM1 pretreatment on EtOH-induced changes in the incorporation of various FFA into cerebral PL in mice. Consistent with our earlier findings, the results suggest that chronic EtOH exposure alters the incorporation of unsaturated fatty acids into phosphatidylinositol (PI), phosphatidylserine, and phosphatidylcholine (PC), but not into phosphatidylethanolamine (PE). No significant differences were observed with stearic acid. The ganglioside GM1 treatment led to increased incorporation of linoleic acid (LA) into PE and PC and appeared to enhance the EtOH-produced effects especially for docosahexaenoic acid (DHA) and to a lesser extent for oleic acid, LA, and arachidonic acid, when compared to the untreated control group. However, when comparison was made with the EtOH-alone group, significant differences were observed only with DHA incorporation and mainly into PE and PI. Thus acyltransferases may play an important role in membrane adaptation to the injurious effects of EtOH and GM1 appears to enhance selective incorporation of FFA into membrane PL; a process that may represent a repair mechanism.     

Amygdala kindling-resistant (SLOW) or -prone (FAST) rat strains show differential fear responses

The authors compared two rat strains, selectively bred for their susceptibility to amygdala kindling, with respect to their performance on various behavioral and learning tasks that are associated with fear and anxiety. The two rat strains differed significantly in measurements of exploration of novel and familiar environments, as well as in reactivity to footshock and fear-based learning. The kindling-resistant (SLOW) strain exhibited a lower ratio of open- to closed-arm entries in the elevated plus-maze, less activity over days in the open field, greater behavioral suppression in the open-field if previously footshocked, greater freezing in the inhibitory avoidance task, and slower acquisition and poorer retention in the one-way avoidance task than did the kindling-prone (FAST) strain. These experiments suggest that the SLOW rats are more expressively fearful than the FAST rats, particularly with respect to environmentally triggered freezing or immobility. Further, these observations imply that the relatively constrained excitability of the amygdala network in the SLOW rats might mediate their relatively greater expression of fear and anxiety compared with the FAST rats.     

V(H) repertoire of a marsupial (Monodelphis domestica)

We have been using a genetic strategy to define the contribution of specific candidate genes, such as those encoding subunits of the gamma-aminobutyric acid type A receptor, to various ethanol sensitive responses. We have used the gene knockout approach in mouse embryonic stem cells to create mice in which the gene encoding the alpha6 subunit of the gamma-aminobutyric acid type A receptor is rendered nonfunctional. In the present report, we provide a detailed characterization of several behavioral responses to ethanol in these null allele mice. In a separate series of experiments, behavioral response to ethanol was compared between two inbred strains of mice that are commonly used as background stock in knockout experiments, namely C57BL/6J and Strain 129/SvJ. Wild type (alpha6+/+) and homozygous null allele (alpha6-/-) mice did not differ to the ataxic effects of ethanol on acute functional tolerance (95.8 +/- 8.7 vs. 98.8 +/- 5.7 mg/dl +/- SEM, respectively). Withdrawal hyperexcitability was assessed following chronic exposure to ethanol vapor (EtOH) or air (CONT) in inhalation chambers in a multiple withdrawal treatment paradigm. At the end of the last treatment cycle, mice were scored for handling induced convulsions (HIC). After adjusting for differences in blood ethanol concentration between genotypes at the end of the final treatment cycle, we observed a greater area under the 24-hr HIC curves in mice treated with ethanol (p < 0.0001) but did not detect an effect of genotype (alpha6+/+/CONT 3.1 +/- 2.0; alpha6-/-/CONT 5.5 +/- 2.5; alpha6+/+/EtOH 30.1 +/- 6.2; alpha6-/-/EtOH 33.0 +/- 5.8 mean units +/- SEM). We also examined these mice for differences in protracted tolerance; at approximately 26 hr into the final withdrawal cycle, each mouse was injected with ethanol (3.5 mg/g body weight) and sleep time was measured. We detected a significant effect of treatment (p < 0.001) with ethanol-treated mice demonstrating signs of tolerance as reflected by a reduction in duration of sleep time. However, effect of genotype was not significant (alpha6+/+/CONT 57.4 +/- 7.6; alpha6-/-/CONT 59.0 +/- 7.6; alpha6+/ +/EtOH 34.8 +/- 7.4; alpha6-/-/EtOH 30.8 +/- 5.6 min +/- SEM). From these data we conclude that the alpha6 subunit of the GABA(A)-R exerts little if any influence on acute functional tolerance, withdrawal hyperexcitability, or protracted tolerance. Strain 129/SvJ and C57BL/6J mice were also compared for acute functional tolerance and were found not to differ (96.3 +/- 4.4 vs. 94.8 +/- 11.3 mg/dl +/- SEM, respectively). Withdrawal hyperexcitability was assessed by comparing the area under the 24 hr HIC curves. Strain 129/SvJ mice displayed a much greater basal HIC response compared to C57BL/6J mice (19.8 +/- 4.3 vs. 0.2 +/- 0.2 mean units +/- SEM, respectively); after adjusting for differences in blood ethanol concentration between strains at the end of the final ethanol treatment cycle, the HIC response was markedly enhanced by ethanol treatment in Strain 129/SvJ mice but not in C57BL/6J mice (50.4 +/- 3.1 vs. 9.5 +/- 5.4 mean units +/- SEM, respectively). The effects of treatment (p < 0.0001), strain (p < 0.0001), and the interaction of strain with treatment (p < 0.01) were significant. Since many gene knockout mice are maintained on a mixed genetic background of Strain 129/SvJ and C57BL/6J, we conclude that significant differences in tests of withdrawal hyperexcitability may be confounded by the influence of genes that cosegregate with the gene targeted allele.     

Ethanol-related traits in mice selectively bred for differential sensitivity to methamphetamine-induced activation.

Acute drug stimulation has been proposed to be an endophenotype for drug abuse. The authors previously reported the short-term selective breeding of lines of mice for low (LMACT) and high (HMACT) stimulation to methamphetamine (MA). These mice were used to examine whether common genes influence the locomotor response to MA and ethanol. Additionally, the authors tested these mice for ethanol drinking, locomotor sensitization, and clearance. LMACT mice were less stimulated by ethanol and consumed more ethanol than HMACT mice, but the lines did not differ in ethanol-induced sensitization. A small difference in ethanol clearance rate (0.1 mg/ml/h) likely had little impact on behavior. Some common genes may influence the locomotor response to MA and ethanol, as well as ethanol drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of arachidonic acid-specific phospholipase A2 in human neuroblastoma cells after chronic alcohol exposure: prevention by GM1 ganglioside

Human neuroblastoma cells were exposed to ethanol (EtOH; 100 mM) in culture for various time periods. It was found that chronic EtOH exposure increased the arachidonyl-specific phospholipase A2 (PLA2) activity significantly in both cytosol (1.6-fold) and membrane (2.2-fold) fractions when 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine was used as a substrate. This arachidonyl-specific PLA2 activity progressively increased with increasing duration of EtOH exposure and reached peak level at 72-hr EtOH exposure (chronic). A significant amount of the PLA2 activity was associated with the membrane fraction. No significant difference in PLA2 activity was observed when 1-palmitoyl-2 oleoyl or linoleoyl-sn-glycero-3-phosphocholine was used as a substrate. It was also found that co-treatment of neuroblastoma cells with ganglioside GM1 reduced the EtOH-induced activation of arachidonyl-specific PLA2 activity. The present results indicate that arachidonic acid-specific PLA2 may play a role in adaptation mechanisms to chronic EtOH in cultured neuroblastoma cells. Ganglioside GM1, in part, may exert its neuroprotective effects by modulating arachidonyl-specific PLA2 activity in chronic EtOH-exposed neuroblastoma cells.     

Does dizocilpine (MK-801) selectively block the enhanced responsiveness to repeated amphetamine administration?

In order to examine the hypothesis that N-methyl-{d}-aspartate (NMDA) receptors are selectively involved in the development of stimulant sensitization, we characterized the interaction between acute and chronic dizocilpine (MK-801)?+?amphetamine using a detailed behavioral analysis, including concurrent assessment of the locomotor and stereotypy components of the stimulant response and continuous monitoring of all the various phases of the emergent sensitization. The results showed that MK-801 (0.125 mg/kg) significantly affected the acute response to amphetamine (0.5, 1.75, 4.0 mg/kg), increasing or decreasing locomotor activity depending on dose. Repeated administration of MK-801?+?amphetamine resulted in a suppression of stereotyped behaviors and a potentiated locomotor sensitization. These findings suggest that rather than blocking the development of sensitization, MK-801 pretreatment may produce a unique behavioral augmentation that is apparent during coadministration and that persists for up to 48 hr in the response to amphetamine challenge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Screening for ENU-induced mutations in mice that result in aberrant ethanol-related phenotypes.

One way to investigate the genetic underpinnings of ethanol-related phenotypes is to create random mutations and screen the mutagenized mice for their behavioral phenotypes. The purposes of this article are to assess the efficacy of a novel high throughput screen to detect known strain differences and to provide evidence of the ability of this screen to detect phenodeviants, as illustrated by two new lines of mutant mice. All mice were tested for the following phenotypes after a dose of 2.25 g/kg of ethanol: ataxia, anxiolytic response, locomotor activity, core body temperature, and blood ethanol concentration, as well as ethanol consumption based on a two-bottle choice test. The authors obtained several baseline measures that allowed for the detection of phenodeviants on these measures as well. To validate this screen, A/J, DBA/2J, and C57BL/6J mouse strains were tested, and previously reported strain differences were found in all phenotypes except ethanol-induced hypothermia. Additionally, two mutant pedigrees were identified: 7TNJ, which exhibited abnormal ethanol-induced locomotor activity, and 112TNR, which exhibited an enhanced ability on the rotarod. These data demonstrate the efficacy of this screen to detect known as well as novel phenotypic differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Demonstration of a carrier state for Cowdria ruminantium in wild ruminants from Africa

We recently conducted a study of the behavioral effects of combined cocaine and ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2) were tested in an automated activity monitor on 2 consecutive days. On day 1, all animals received an IP injection of sterile saline and were placed into the activity monitor for 30 min. Behaviors measured were total distance traveled, stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again for 15 min following injection of one of the following: saline, 10% v/v ethanol at 2.0 g kg(-1) or 2.0 g kg(-1) ethanol plus 5, 15, or 30 mg kg(-1) cocaine. Cocaine alone at the same doses was injected into separate groups of animals. For the B6 strain, the overall effect of ethanol was to reduce cocaine-induced locomotor stimulation; no consistent effect of ethanol on cocaine-induced locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in both strains and sexes was partially reversed by ethanol. Ethanol also partially reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice, cocaine-increased wall seeking tended to be reversed by coadministration of ethanol, whereas no consistent pattern was observed in the D2s. Results from this study suggest that the several measures affected by cocaine (locomotor activity, stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by concurrent treatment with ethanol. Furthermore, our results point to genetic-based differences in ethanol's effects on cocaine-related behaviors. We address the implications for combined ethanol and cocaine use in humans.     

Age differences in ethanol-induced hypothermia and impairment in mice

This experiment examined the effects of ethanol on body temperature and ethanol-induced impairment among three different age groups (8 months, 18 months, and 28 months) of C57BL/6NNIA male mice. Mice were injected intraperitoneally with 3 g/kg ethanol or an equivalent volume of saline. Body temperature, blood ethanol levels, and time when the righting response (RR) was lost and regained were measured. Body temperature also was measured prior to injection and at 30 and 120 min post-injection The aged mice showed less ethanol-induced hypothermia but were impaired longer as compared to the younger mice. Blood ethanol levels at loss and regaining of the RR were lower for old mice than the younger mice. Body temperature for the youngest group was lower at each time of measurement as compared to the older groups. Age differences in body temperature prior to ethanol or saline injection were small and nonsignificant.