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Increased behavioral responses to ethanol in Lmo3 knockout mice.
Genes Brain Behav 2014; 13(8):777-83GB

Abstract

LIM-domain-only 3 (LMO3) is a transcriptional regulator involved in central nervous system development and neuroblastoma. Our previous studies implicated a potential role for LMO3 in regulating ethanol sensitivity and consumption. Here, we examined behavioral responses to ethanol in a line of Lmo3 null (Lmo3(Z)) mice, utilizing the ethanol-induced loss-of-righting-reflex (LORR) test, two-bottle choice ethanol consumption and the drinking in the dark (DID) test, which models binge-like ethanol consumption. We found that Lmo3(Z) mice exhibited increased sedation time in response to ethanol in the LORR test and drank significantly more ethanol in the DID test compared with their wild-type counterparts, but showed no differences in two-bottle choice ethanol consumption. To explore where LMO3 may be acting in the brain to produce an ethanol phenotype, we also examined reporter gene (β-galactosidase) expression in heterozygous Lmo3(Z) mice and found strong expression in subcortical areas, particularly in those areas implicated in drug abuse, including the nucleus accumbens (Acb), cortex, hippocampus and amygdala. We also examined Lmo3 expression in the brains of wild-type mice who had undergone the DID test and found a negative correlation between Lmo3 expression in the Acb and the amount of ethanol consumed, consistent with the increased binge-like drinking observed in Lmo3(Z) mice. These results support a role for LMO3 in regulating behavioral responses to ethanol, potentially through its actions in the Acb.

Authors+Show Affiliations

Department of Psychiatry and Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25176312

Citation

Savarese, A, et al. "Increased Behavioral Responses to Ethanol in Lmo3 Knockout Mice." Genes, Brain, and Behavior, vol. 13, no. 8, 2014, pp. 777-83.
Savarese A, Zou ME, Kharazia V, et al. Increased behavioral responses to ethanol in Lmo3 knockout mice. Genes Brain Behav. 2014;13(8):777-83.
Savarese, A., Zou, M. E., Kharazia, V., Maiya, R., & Lasek, A. W. (2014). Increased behavioral responses to ethanol in Lmo3 knockout mice. Genes, Brain, and Behavior, 13(8), pp. 777-83. doi:10.1111/gbb.12176.
Savarese A, et al. Increased Behavioral Responses to Ethanol in Lmo3 Knockout Mice. Genes Brain Behav. 2014;13(8):777-83. PubMed PMID: 25176312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased behavioral responses to ethanol in Lmo3 knockout mice. AU - Savarese,A, AU - Zou,M E, AU - Kharazia,V, AU - Maiya,R, AU - Lasek,A W, Y1 - 2014/09/24/ PY - 2014/04/29/received PY - 2014/08/20/revised PY - 2014/08/29/accepted PY - 2014/9/2/entrez PY - 2014/9/2/pubmed PY - 2015/7/24/medline KW - Binge drinking KW - LMO3 KW - ethanol KW - sedation SP - 777 EP - 83 JF - Genes, brain, and behavior JO - Genes Brain Behav. VL - 13 IS - 8 N2 - LIM-domain-only 3 (LMO3) is a transcriptional regulator involved in central nervous system development and neuroblastoma. Our previous studies implicated a potential role for LMO3 in regulating ethanol sensitivity and consumption. Here, we examined behavioral responses to ethanol in a line of Lmo3 null (Lmo3(Z)) mice, utilizing the ethanol-induced loss-of-righting-reflex (LORR) test, two-bottle choice ethanol consumption and the drinking in the dark (DID) test, which models binge-like ethanol consumption. We found that Lmo3(Z) mice exhibited increased sedation time in response to ethanol in the LORR test and drank significantly more ethanol in the DID test compared with their wild-type counterparts, but showed no differences in two-bottle choice ethanol consumption. To explore where LMO3 may be acting in the brain to produce an ethanol phenotype, we also examined reporter gene (β-galactosidase) expression in heterozygous Lmo3(Z) mice and found strong expression in subcortical areas, particularly in those areas implicated in drug abuse, including the nucleus accumbens (Acb), cortex, hippocampus and amygdala. We also examined Lmo3 expression in the brains of wild-type mice who had undergone the DID test and found a negative correlation between Lmo3 expression in the Acb and the amount of ethanol consumed, consistent with the increased binge-like drinking observed in Lmo3(Z) mice. These results support a role for LMO3 in regulating behavioral responses to ethanol, potentially through its actions in the Acb. SN - 1601-183X UR - https://www.unboundmedicine.com/medline/citation/25176312/Increased_behavioral_responses_to_ethanol_in_Lmo3_knockout_mice_ L2 - https://doi.org/10.1111/gbb.12176 DB - PRIME DP - Unbound Medicine ER -