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RSA 2007 Abstracts
Oregon Health & Science University
HYBRID C57BL/6J X FVB/NJ MICE DO NOT SELF-INFUSE MORE ETHANOL THAN DO C57BL/6J MICE: T. L. Fidler; A. M. Struthers; M. S. Powers; C. L. Cunningham. Oregon Health & Science University, Portland, OR 97239.H
Across many studies, C57BL/6J (B6) mice have been identified as the highest ethanol drinkers when compared to a number of other strains. However, Blednov and colleagues (2005) reported that the F1 hybrids of B6 and FVB/NJ (FVB) mice consumed more ethanol than B6 mice across multiple access schedules. We included these three strains in an experiment using intragastric (IG) self-infusion of ethanol to see if the difference in ethanol intake would still be observed when ethanol’s usual taste and odor cues were removed. Mice were surgically implanted with chronic IG catheters and allowed to recover. Initially Group E mice from each strain received a series of 3 passive infusions per day (2.5-4.5 g/kg/infusion) over a period of 5 days. Control mice (Group C) from each strain received passive infusions of water during this phase. During subsequent self-infusion phases mice had access (23 h/day) to one or two Kool-Aid solutions presented in drinking tubes without ethanol. During the No-Choice phase, only one flavor was available and licks produced IG ethanol infusions (20% v/v). For the choice phase, a second flavor was added and licks on this flavor were paired with infusions of water. During both self-infusion phases, Group E mice from all three strains self-infused more ethanol than Group C mice. Moreover, B6 mice self-infused more ethanol than either the FVB or F1 mice (which did not differ from each other) during both no-choice and choice self-infusion phases. B6 mice also had the most ethanol bouts and the highest preference for the ethanol-paired flavor. The difference in results between Blednov et al.’s drinking study and our IG self-infusion experiment suggests that ethanol-intake is controlled by different factors (taste or pharmacology) depending on the route of administration. Supported by NIAAA U01-AA13479-INIA.
ETOH WITHDRAWAL PRODUCES A DEFICIT IN ACCELERATING ROTAROD PERFORMANCE IN MICE: S. D. Philibin; A. J. Cameron; J. C. Crabbe. Oregon Health & Science University, Department of Behavioral Neuroscience, Portland Alcohol Research Center and VA Medical Center, Portland, OR, 97239.
EtOH withdrawal produces various behavioral effects in mice, including handling induced convulsions, anxiety-like behaviors and decreased locomotor activity. Exposure to EtOH vapor by inhalation is an effective means for induction of physical dependence. While some recent EtOH vapor inhalation studies use chronic intermittent EtOH exposure, continuous 72 hr EtOH exposure is traditionally used. We used both chronic intermittent and chronic EtOH exposure to assess the effects of withdrawal on accelerating rotarod (ARR) acquisition, a simple motor learning task. Genetically heterogeneous outbred male mice were assigned to either EtOH or non-EtOH treatment groups. Mice exposed to three cycles of 16 hr EtOH and 8 hr periods of air were compared for ARR acquisition vs. control groups at 8 hr after withdrawal. One-way ANOVA revealed a smaller increase in latency to fall between the average of the first two trials and the average of the last two trials in EtOH withdrawing mice (F1,19 = 15.09; p < 0.01), indicating they learned less over the 8 trials. In a separate experiment, mice exposed to EtOH vapor continuous for 72 hr were compared for ARR acquisition vs. control groups. Mice were given 3 trials at 8, 10, and 12 hrs after withdrawal, and then 10 trials at 24 hr. Repeated-measures one-way ANOVA revealed that EtOH withdrawing mice had shorter latency to fall from the ARR (F1, 18 = 5.90; p < 0.05) and that there was a significant effect of time (F3, 54 = 28.72; p < 0.01) with maximal disruption at 10 hr. These data demonstrate that withdrawal from chronic intermittent or chronic EtOH exposure produces a deficit in ARR performance. Furthermore, withdrawal severity after 72 hr of chronic EtOH exposure was time dependent. These data suggest that ARR performance offers a simple measure of EtOH withdrawal effects on behavior.
Supported by grants AA10760, AA13519, AA07468 and the Department of Veterans Affairs.
NEW TARGETS FOR INTERVENTION: ADDICTION TO 24-HR TWO-BOTTLE CHOICE DRINKING AND C57BL/6 MICE: C. L. Cunningham; T. L. Fidler.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR.Alcohol research is mired in a rut. This rut is created by the addiction of alcohol scientists to excessive use of one popular phenotype, 24 hr 2-bottle choice drinking/preference, and one popular genotype, the C57BL/6 (B6) inbred mouse. The reasons behind this compulsive uncontrollable behavior seem simple: choice drinking is easy/inexpensive to measure and B6 mice consume larger volumes and show a greater preference for 10% ethanol than most other inbred mice. However, progress has been hampered by over-reliance on this single phenotype and single genotype. Despite nearly a half-century of research, we still do not know why B6 mice show high intakes in this procedure or whether the underlying mechanisms are similar to those responsible for excessive intake of ethanol in human alcoholics. Unfortunately, we have become tolerant to this adverse consequence of our addiction and we remain dependent on this phenotype and genotype. To escape the rut, we must increase our use of other phenotypes and genotypes. This presentation will emphasize two alternative phenotypes, both of which are sensitive to differences among mouse genotypes. The first is a model of intra-gastric self-infusion of ethanol in which mice that have previously been exposed to passively infused ethanol or water are then allowed to self-infuse ethanol or water by licking tubes that contain different flavored solutions. Using this procedure, we have found that a strain that is normally reluctant to drink ethanol in the home cage (DBA/2) is able to self-infuse ethanol at levels similar to those of B6 mice in a standard drinking procedure. Moreover, in contrast to B6 mice, these mice show a binge-like pattern of intake that may more closely resemble the drinking phenotype of human alcoholics. The second phenotype is conditioned place preference, a procedure in which mice learn to approach distinctive contextual cues that have been paired with ethanol injection. Expression of this behavior may represent an animal model of cue-elicited craving. Recent examples of studies involving both phenotypes will be presented. Audience members will be strongly encouraged to resist the urge to place drinking bottles on the home cages of B6 mice. Supported by AA07702 & AA13479.
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