The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat diving model.
1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled pool from a hidden platform, without stereotyped behavior. 2. The sigma-selective ligand, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethyl-amine monohydrochloride), attenuates the effects of PCP in this procedure. 3. The serotonin2 (5-HT2) antagonist, ritanserin, and the sigma receptor ligands, 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine HBr (Dup734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1- (cyclopropylmethyl)piperidine (XJ448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802) and rimcazole similarly attenuate the effects of PCP. 4. The dopamine D2/sigma ligands, haloperidol and cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4- methylaminobenzamide (YM-09151-2) completely reverse the effects of PCP, whereas the same dose ranges of these drugs produce sedation. 5. The dopamine D2-selective antagonist, sulpiride, has no apparent effect on the PCP latency to the rat dive. 6. Thus, PCP-induced diving behavior was improved by sigma ligands and the 5-HT2 antagonist. This model of negative symptoms in an experimental animal will facilitate experiments on drug treatments for schizophrenia.
Ogawa
S
S
Department of Pharmacology, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
Okuyama
S
S
Tsuchida
K
K
Araki
H
H
Otomo
S
S
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004242:Diving; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects*
D000840:Anisoles; D002227:Carbazoles; D010880:Piperidines; D011437:Propylamines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C078773:DuP 734; C034931:rimcazole; D010622:Phencyclidine