PHARMACOLOGICAL EVIDENCE FOR THE INVOLVEMENT OF SIGMA-SITES IN DTG-INDUCED CONTRALATERAL CIRCLING IN RATS

The central distribution of sigma sites labelled by di-o-tolylguanidin e (DTG), a compound which has specific affinity for sigma sites, and i ts ability to produce postural movements, are consistent with the hypo thesis that sigma sites may play a functional role in the regulation o f movement. The aim of the present study was to evaluate the specifici ty of the circling behaviour induced by unilateral intranigral injecti on of DTG in rats. As previously described, DTG produced dose-dependen t unilateral rotations (2.5-20 nmol/rat). A similar dose-dependent cir cling behaviour was observed with DMTG and (+) NANM (3-40 nmol/rat), c ompounds which bind to both sigma and PCP sites, and with haloperidol (3-20 nmol/rat) whereas raclopride and D,L-sulpiride did not elicit an y circling (10 nmol/rat). DTG-induced circling after intranigral injec tion (10 nmol/rat) was decreased in a dose-dependent manner by rimcazo le (20-40 mg/kg, i.p.), a selective ligand for sigma sites, and by BMY 14802 (3, 10, 30 mg/kg, i.p.), ifenprodil and eliprodil (1, 3, 10 mg/ kg, i.p.), non-selective sigma ligands. In contrast, naloxone (1 mg/kg , s.c.) and CGS 19755 (1, 3, 10 mg/kg, i.p.) did not change the DTG-in duced circling. Eliprodil failed to inhibit circling produced by compo unds devoid of any affinity for sigma sites such as APV, dizocilpine o r muscimol, indicating the specificity of the inhibition observed with eliprodil on the DTG-induced circling. These results suggest that cir cling behaviour produced by unilateral intranigral injection of DTG ma y be a useful model for studying the interaction of new drugs with sig ma sites and might also be used to investigate further the potential i nvolvement of these sites in the regulation of the activity of the nig ro-striatal dopaminergic pathways.