Hyperlocomotion in rats by two sigma ligands (+)-3-PPP and (+)-SKF 10,047

• Published in: Japanese Journal of Pharmacology Vol. 61; no. suppl.1; p. 180
• Main Authors: Hirotsu, Ichiro, Honbo, Naomi, Hayashi, Yasuhiro, Ohno, Tomochika
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1993
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)51599-2

There is now evidence for the existence of two subtypes of sigma sites, termed sigma-1 and sigma-2, whose role in brain function, however, remains obscure. In order to clarify their functional role, we examined the effects of a nondiscriminant ligand (+)-3-PPP (high affinities at sigma-1 and sigma-2) and a discriminant ligand (+)-SKF 10,047 (high affinity at sigma-1) by comparing their respective (-) isomers (low affinities at both sigma sites) on the spontaneous locomotor activity in rats. The (+) isomers (10 mg/kg, s.c.) produced hyperlocomotion, while (-) isomers (10 mg/kg, s.c.) had no or iittle effects on spontaneous locomotor activities. The hyperlocomotion by (+)-3-PPP (30 mg/kg, s.c.) and (+)-SKF 10,047 (10 mg/kg, s.c.) was inhibited by the pretreatment with a sigma antagonist BMY 14802 (30 mg/kg, p.o.). Moreover, (+)-3-PPP did not cause hyperlocomotion in reserpinized rats. The (+)-3-PPP effect was antagonized by a D_2 antagonist sulpiride (30 mg/kg, p.o.), but the pretreatment with an α-antagonist phenoxybenzamine (10 mg/kg, i.p.) was without effect. These results indicate that hyperlocomotion induced by these sigma ligands may be mediated via sigma-1 site, and presynaptically modulate dopaminergic system.