The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat diving model

Abstract

1. 1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled pool from a hidden platform, without stereotyped behavior. 2. 2. The sigma-selective ligand, NE-100 ( N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride), attenuates the effects of PCP in this procedure. 3. 3. The serotonin 2 (5-HT 2) 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), α-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802) and rimcazole similarly attenuate the effects of PCP. 4. 4. The dopamine D 2/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. 5. The dopamine D 2-selective antagonist, sulpiride, has no apparent effect on the PCP latency to the rat dive. 6. 6. Thus, PCP-induced diving behavior was improved by sigma ligands and the 5-HT 2 antagonist. This model of negative symptoms in an experimental animal will facilitate experiments on drug treatments for schizophrenia.