CHANGES IN REGIONAL GLUCOSE-METABOLISM AND BEHAVIOR FOLLOWING INTRANIGRAL APPLICATION OF THE KAPPA-OPIATE AGONIST U50,488

The autoradiographic distribution (1) and relative isolation of prodyn orphin peptides in the substantia nigra pars reticulata provide a mode l system for understanding the function of these substances (2). The u se of kappa selective ligands, such as U50,488, provides a means for a ctivating neuronal substrates in the SNR that normally respond to the secretory products of prodynorphin peptides. In this study, the 2-deox y-D-[1-C-14]glucose method, adapted for use in freely moving rats, was used to study kappa-mediated changes in brain functional activity ind uced by microinjection of U50,488 in the SNR. The kappa agonist induce d dose-dependent contralateral rotational behavior, confirming the pot ent locomotor stimulation produced by this ligand. In general, intrani gral U50,488 induced decreases in local cerebral glucose utilization i n basal ganglia and related circuitry, consistent with the observed mo tor effects. U50,488-treated animals exhibited significant alterations in LCGU ipsilateral relative to contralateral to the injection site ( PN, SC, LGN). Relative to controls, significant decreases in LCGU were observed ipsilaterally (PN, FG, VTA, RN), contralaterally (DT, CP, PA R), and bilaterally (PPN, IC, SNC, SNR, GP, CG) These findings suggest that the [C-14]DG method Is useful in elucidating anatomical substrat es of circling behavior that are activated downstream of intial kappa receptor interactions in the SNR.