Genetic Mapping of Vocalization to a Series of Increasing Acute Footshocks Using B6.A Consomic and B6.D2 Congenic Mouse Strains

Matthews, Douglas B.; Chesler, Elissa J.; Cook, Melloni N.; Cockroft, Judy; Philip, Vivek M.; Goldowitz, Dan

doi:10.1007/s10519-008-9210-7

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…This could suggest that acute withdrawal reduces sensitivity to the US; however, acute withdrawal has also been shown to decrease locomotion (Karadayian and Cutrera, 2013), suggesting that movement-based measures may be inaccurate. Typically, these strains respond to increasing footshocks with locomotor changes (startle, running, jumping) followed by vocalization at higher levels (Liu et al, 2003; Matthews et al, 2008), and the threshold is defined as the first observable locomotor response; however, when the threshold data were re-analyzed to assess the point at which any response (locomotor or vocalization) was observed, the treatment differences in both strains were non-significant (p>0.07 for all measures), suggesting that the footshock threshold is not altered by acute withdrawal, although the pattern of responding is.…”

Section: Resultsmentioning

confidence: 99%

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

Tipps

Raybuck

Buck

et al. 2015

Alcoholism Clin & Exp Res

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Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes.

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Section: Resultsmentioning

confidence: 99%

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

Tipps

Raybuck

Buck

et al. 2015

Alcoholism Clin & Exp Res

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“…Housing and testing environment conditions were maintained throughout testing. Except where noted, BXD RI lines were imported into the Russell Vivarium at Oak Ridge National Laboratory (ORNL) for environmentally controlled, year round breeding and distribution for all assays except for handling-induced convulsion (HIC) and footshock vocalization, for which mice were bred at University of Tennessee Health Science Center (UTHSC) and housed as described in Matthews et al (2008) . Litters were weaned at about 3 weeks of age and shipped to various test sites in the TMGC's climate controlled, specific pathogen-free (SPF) mouse transport van at about 6–7 weeks of age, allowing at least 1 week of acclimation to their new home colony.…”

Section: Methodsmentioning

confidence: 99%

High‐throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains

Philip

Duvvuru

Gomero

et al. 2010

Genes Brain and Behavior

178

267

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Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4-methylenedioxymethamphetamine; “ecstasy” (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.

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“…Each subsequent shock was progressively higher, increasing in increments of 0.05 mA until the animal vocalized. The shock level at which the animal vocalized was recorded for analysis (Matthews et al 2008).…”

Section: Methodsmentioning

confidence: 99%

Heterozygous deletion of NR1 subunit of the NMDA receptor alters ethanol-related behaviors and regional expression of NR2 subunits in the brain

Elberger

Matthews

et al. 2012

Neurotoxicology and Teratology

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NMDA receptors have been hypothesized to play a role in various aspects of ethanol-related phenotypes, notably in ethanol withdrawal. However, the role of each of the specific subunits remains unclear. To address this issue, mice that are heterozygous for the NR1 deletion, and thus have a reduction in functional NMDA receptors, were examined for ethanol consumption and acute ethanol withdrawal. Additionally, mice were examined for the level of vocalization following footshock, and behavior in an elevated plus maze, to determine their responses to stress. In these behavioral tests, NR1 heterozygous mice were shown to consume significantly higher levels of ethanol in the two bottle-choice test showing a possible role for this receptor in ethanol consumption. Analysis of acute withdrawal found that the heterozygous mice exhibit lower levels of handling-induced convulsions consistent with a role in ethanol sensitivity or withdrawal. In contrast, no effects on stress-related phenotypes were detected. Levels of NR2A-NR2D subunits of the NMDA receptor in specific brain regions were compared between NR1+/- mice and wild-type controls to assess whether the behavioral responses were specific to the diminution in NR1 expression or whether these changes could be due to secondary changes in expression of other NMDA subunits. Real-time quantitative PCR, Western blot and immunohistochemistry were used to examine expression levels in the hippocampus, neocortex, striatum and cerebellum. For the majority of the subunits, no differences were found between the wild-type and heterozygous mice in any of the brain regions. However, the NR2B subunit exhibited differences in expression of RNA in the hippocampus and protein levels in multiple brain regions, between wild-type and NR1+/- mice. These results show that NR1 plays a role, through mechanisms as yet unknown, in the expression of NR2 subunits in a region and subtype specific manner. This provides evidence of the effects of altered levels of NR1 expression on ethanol withdrawal and consumption, and suggests that concomitant changes in the levels of NR2B may contribute to that effect.

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Genetic Mapping of Vocalization to a Series of Increasing Acute Footshocks Using B6.A Consomic and B6.D2 Congenic Mouse Strains

Cited by 7 publications

References 30 publications

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

High‐throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains

Heterozygous deletion of NR1 subunit of the NMDA receptor alters ethanol-related behaviors and regional expression of NR2 subunits in the brain

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