Cocaine effects on gene regulation in the striatum and behavior: increased sensitivity in D3 dopamine receptor-deficient mice

Neuroreport. 2000 Aug 3;11(11):2395-9. doi: 10.1097/00001756-200008030-00012.

Abstract

Central effects of psychostimulants such as cocaine are predominantly mediated by dopamine receptors. We have used mice with a targeted deletion of the D3 dopamine receptor subtype to investigate the role of this receptor in the regulation of gene expression in striatal neurons and behavior by acute and repeated treatment with cocaine (25 mg/kg). In mice lacking D3 receptors, acute administration of cocaine has more pronounced stimulatory effects on c-fos and dynorphin expression in the dorsal and ventral striatum. The behavioral response to cocaine is also increased in these mice. These findings indicate that the D3 receptor plays an inhibitory role in the action of cocaine on behavior and gene regulation in the striatum.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / pathology
  • Cocaine-Related Disorders / physiopathology
  • Dynorphins / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Head Movements / drug effects
  • Head Movements / physiology
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neostriatum / cytology
  • Neostriatum / drug effects*
  • Neostriatum / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Dopamine D2 / deficiency*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D3
  • Stereotyped Behavior / drug effects
  • Stereotyped Behavior / physiology

Substances

  • Drd3 protein, mouse
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Dynorphins
  • Cocaine