Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats.

Abstract

We evaluated correlation between neurochemical and functional alterations of the nigrostriatal dopaminergic system in rat brains lesioned with 6-hydroxydopamine (6-OHDA), that model hemi-Parkinson's disease (PD), by using three different quantitative in vivo and in vitro methods. Rats unilaterally lesioned with different doses of 6-OHDA underwent two types of in vivo experiments: (1) a rotational behavioral study with methamphetamine (MAP) or apomorphine (APO); and (2) a positron emission tomography (PET) study with [11C]PE2I (radioligand for dopamine transporters) or [11C]raclopride (radioligand for dopamine D2 receptors). An in vitro autoradiographic study with the same radioligands was also conducted. The number of rotations after the MAP or APO injection increased with increased doses of 6-OHDA. The in vitro and in vivo binding of [11C]PE2I dose-dependently decreased in response to the 6-OHDA injections, while that of [11C]raclopride dose-dependently increased. There was a significant negative hyperbolic correlation between the number of rotations after MAP injection and the binding of [11C]PE2I. In contrast, there was a significant positive linear correlation between the number of rotations after APO injections and the binding of [11C]raclopride. These results robustly reveal a molecular pharmacological basis of parkinsonian symptoms in animal models of PD, and indicate the utility and validity of in vivo PET measurements in assessing pre- and post-synaptic dopaminergic functions.