Lmo4 in the nucleus accumbens regulates cocaine sensitivity.
An estimated 2 million Americans use cocaine, resulting in large personal and societal costs. Discovery of the genetic factors that contribute to cocaine abuse is important for understanding this complex disease. Previously, mutations in the Drosophila LIM-only (dLmo) gene were identified because of their increased behavioral sensitivity to cocaine. Here we show that the mammalian homolog Lmo4, which is highly expressed in brain regions implicated in drug addiction, plays a similar role in cocaine-induced behaviors. Mice with a global reduction in Lmo4 levels show increased sensitivity to the locomotor stimulatory effects of cocaine upon chronic cocaine administration. This effect is reproduced with downregulation of Lmo4 in the nucleus accumbens by RNA interference. Thus, Lmo genes play conserved roles in regulating the behavioral effects of cocaine in invertebrate and mammalian models of drug addiction.
Lasek
A W
AW
The Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA, USA. alasek@gallo.ucsf.edu
Kapfhamer
D
D
Kharazia
V
V
Gesch
J
J
Giorgetti
F
F
Heberlein
U
U
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003042:Cocaine / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D042282:Microdissection; D009043:Motor Activity / Q000187:drug effects; D016254:Mutagenesis, Insertional; D009714:Nucleus Accumbens / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013238:Stereotaxic Techniques; D014157:Transcription Factors / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018765:Dopamine Uptake Inhibitors; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D014157:Transcription Factors; D012313:RNA; D001616:beta-Galactosidase; D003042:Cocaine