EFFECT OF L-DOPA AND 6-HYDROXYDOPAMINE LESIONING ON [C-11] RACLOPRIDEBINDING IN RAT STRIATUM, QUANTIFIED USING PET

A positron emission tomograph (PET) was used to image D-2 dopamine rec eptor function in rat striata and to obtain regional time-radioactivit y curves from individual rat brains following i.v. injection of carbon -11-labelled raclopride. Despite the limited resolution of the camera, together with associated spillover and partial volume effects, the ki netic data obtained from striata were such that specific binding of th e radioligand could be quantified unilaterally, using a reference tiss ue compartmental model, with cerebellum data as an indirect input func tion. With the exception that the rat is anaesthetised, the experiment al system is analogous to the acquisition and collection of clinical P ET data and, by using animal models of disease, can be used to aid the interpretation of clinical studies. Using g-hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta to produce a rat hemip arkinsonian model, the present results confirm that deafferentation ca uses a supersensitivity of post-synaptic D-2 dopamine receptors. Satur ation studies indicated that the measured 23% increase in [C-11]raclop ride binding potential reflected a change in receptor affinity. Modula tion of extracellular dopamine concentration, monitored by in vivo mic rodialysis, demonstrated that the increased binding was unlikely to be due to a reduction in receptor occupancy by endogenous dopamine. Acut e administration of L-3,4-dihydroxyphenylalanine (L-dopa) also caused an increase in [C-11]raclopride binding potential, confirming the sugg estion that L-dopa plays a more complex role than that of dopamine pre cursor in the nigrostriatal pathway. (C) 1995 Wiley-Liss, Inc.