Elevated dopamine D2High receptors in alpha-1b-adrenoceptor knockout supersensitive mice.
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.
Tassin
Jean-Pol
JP
Institut National de la Santé et de la Recherche Médicale Unité 114 et Centre National de la Recherche Scientifique UMR7148, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Torrens
Yvette
Y
Salomon
Lucas
L
Lanteri
Christophe
C
Seeman
Philip
P
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004294:Domperidone / Q000493:pharmacokinetics; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000187:drug effects; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
C547717:Adra1b protein, mouse; D018492:Dopamine Antagonists; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D004294:Domperidone; D004298:Dopamine