Waved-1 mutant mice are hypersensitive to the locomotor actions of cocaine.
Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes, and is expressed heavily in basal forebrain and striatal regions. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, brain anatomy, biogenic amines, stress response, and behavior are normal prior to, but altered following puberty. As an initial screen for possible alterations in nigrostriatal and mesolimbic dopamine (DA) systems, we tested adult Wa-1 mutant mice in an open field, following acute injection with cocaine (15 mg/kg). Wa-1 mice exhibited significantly greater ambulatory distance, number of ambulatory episodes, and cocaine-induced motor stereotypies than do controls. These data indicate that adult Wa-1 mice are hypersensitive to the locomotor effects of cocaine and provide a new potential link between neurodevelopmental processes and adult psychostimulant responsiveness.
Stanwood
Gregg D
GD
Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. gregg.stanwood@vanderbilt.edu
Levitt
Pat
P
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics*
D018765:Dopamine Uptake Inhibitors; D051300:Wiskott-Aldrich Syndrome Protein Family; D003042:Cocaine