IN-VIVO FUNCTIONAL INTERACTION BETWEEN PHENCYCLIDINE BINDING-SITES AND SIGMA-RECEPTORS TO PRODUCE HEAD-WEAVING BEHAVIOR IN RATS

To investigate the in vivo functional interaction between phencyclidin e (1-(1-phenylcyclohexyl)piperidine; PCP) binding sites and sigma rece ptors, we examined the effects of sigma receptor ligands on stereotype d head-weaving behavior induced by PCP, a putative PCP/sigma receptor ligand, and 1-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imine ((+)-MK -801; dizocilpine), a selective PCP binding site ligand, in rats. PCP (7.5 mg/kg, i.p.)-induced head-weaving behavior was inhibited by both 2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine (NE-100; 0.03-1.0 m g/kg, p.o.), a selective sigma(1) receptor ligand, and orophenyl)-4-(5 -fluoro-2-pyrimidinyl)-1-piperidine butanol (BMY-14802; 3 and 10 mg/kg , p.o.), a prototype sigma receptor ligand, in a dose-dependent manner , whereas NE-100 (0.1-1.0 mg/kg, p.o.) and BMY-14802 (3 and 10 mg/kg, p.o.) did not inhibit dizocilpine (0.25 mg/kg, s.c.)-induced head-weav ing behavior. These results suggest that NE-100 and BMY-14802 act via sigma receptors. Dizocilpine-induced head-weaving behavior was potenti ated by 1,3-di-o-tolyl-guanidine (DTG; 0.03-0.3 mu g/kg, i.v.) and(+)- 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP; 3 and 6 mg/kg, i.p.), sigma(1)/sigma(2) receptor ligands, as well as by (+)-N-allyl-n ormetazocine ((+)-SKF-10,047; 8 mg/kg, i.p.), a sigma(1) receptor liga nd, while DTG (0.3 mu g/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and(+)-SK F-10,047 (8 mg/kg, i.p.) did not induce this behavior. Potentiation of dizocilpine-induced head-weaving behavior by DTG (0.3 mu g/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) was comp letely blocked by NE-100 (0.1 mg/kg, p.o.) and BMY-14802 (10 mg/kg, p. o.). These results suggest that PCP binding sites and sigma receptors are involved in PCP-induced head weaving behavior, and that sigma(1) r eceptors play an important role in modulation of the head-weaving beha vior.