Elevated dopamine D2High receptors in alpha-1b-adrenoceptor knockout supersensitive mice

Synapse. 2007 Jul;61(7):569-72. doi: 10.1002/syn.20401.


Although amphetamine induces hyperactivity by releasing dopamine (DA), mice that lack alpha1b-adrenoceptors do not release DA in response to amphetamine and do not, therefore, exhibit locomotor supersensitivity to amphetamine. However, such mice reveal hyperlocomotion to p-chloroamphetamine (PCA). Because these alpha1b-adrenoceptor knockout mice have no alterations in the striatal densities of DA D1 or D2 receptors, the basis for any possible dopaminergic contribution to the PCA-induced hyperlocomotion to PCA is unclear. Therefore, because supersensitive animals are generally known to have a higher proportion of DA D2 receptors in the high-affinity state for DA D2(High), we investigated whether there was any change in the alpha1b-adrenoceptor knockout striata in the proportion of DA D2(High) receptors to determine whether there could be a DA-based contribution to the PCA-induced hyperlocomotion. We found that the proportion of D2(High) in the wild type striata was 23 +/- 3.3%, whereas that in the alpha1b-adrenoceptor knockout striata was 52 +/- 2.9%, an increase of 2.3-fold. This elevation agrees with other types of DA-supersensitive animal striata and could assist in eliciting a supersensitive response in these alpha1b-adrenoceptor knockout mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Domperidone / pharmacokinetics
  • Dopamine / pharmacology
  • Dopamine Antagonists / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding / drug effects
  • Receptors, Adrenergic, alpha-1 / deficiency*
  • Receptors, Dopamine D2 / metabolism*


  • Adra1b protein, mouse
  • Dopamine Antagonists
  • Receptors, Adrenergic, alpha-1
  • Receptors, Dopamine D2
  • Domperidone
  • Dopamine