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

ABSTRACT

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.