Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET

Receptor supersensitivity is an important concept for understanding neurotr ansmitter and receptor dynamics. Traditionally, detection of receptor super sensitivity has been performed using autoradiography or positron emission t omography (PET). We show that use of magnetic resonance imaging (MRI) not o nly enables one to detect dopaminergic supersensitivity, but that the hemod ynamic time course reflective of this fact is different in different brain regions. In rats unilaterally lesioned with intranigral 6-hydroxydopamine, apomorphine injections lead to a large increase in hemodynamic response (ce rebral blood volume, CBV) in the striato-thalamo-cortico circuit on the les ioned side but had little effect on the intact side. Amphetamine injections lead to increases in hemodynamic responses on the intact side and little o n the lesioned side in the same animals. The time course for the increase i n CBV after either amphetamine or apomorphine administration was longer in striatum and thalamus than in frontal cortex. C-11-PET studies of ligands w hich bind to the dopamine transporter (2-beta-carbomethoxy-3-beta-(4-fluoro phenyl)tropane 1,5-naphthalnendisulfonate, WIN 35, 428 or CFT) and D2 recep tors (raclopride) confirm that there is a loss of presynaptic dopamine term inals as well as upregulation of D2 receptors in striatum in these same ani mals. Pharmacologic MRI should become a sensitive tool to measure functiona l supersensitivity in humans, providing a complementary picture to that gen erated using PET studies of direct receptor binding. (C) 2000 Wiley-Liss, I nc.