Serotonergic involvement in phencyclidine-induced behaviors.
Administration of 5-10 mg/kg of phencyclidine (PCP) caused stereotyped behaviors including sniffing, backpedalling, head weaving and turning in rats. The PCP-induced stereotyped behaviors (backpedalling, head weaving and turning) were attenuated by serotonin (5-HT) depleters [reserpine, p-chlorophenylalanine, p-chloroamphetamine (PCA)] and 5-HT receptor antagonist (cyproheptadine). PCP-induced head weaving and turning were potentiated by 5-HT precursor (tryptophan) and 5-HT releaser (PCA). PCP-induced head weaving were potentiated also by monoamine oxidase inhibitor (pargyline) and 5-HT reuptake inhibitor (imipramine). PCP 5-10 mg/kg significantly increased the content of 5-HT in the thalamus/hypothalamus at 30 and 60 min after the injection, except PCP 5 mg/kg at 60 min. PCP 7.5 and 10 mg/kg increased the rate of increment of 5-HT by pargyline in the thalamus/hypothalamus at 30 and 60 min after the injection, respectively. PCP 10 mg/kg significantly increased the contents of 5-HIAA in the striatum and thalamus/hypothalamus at 30 min, but decreased that of 5-HIAA in all discrete brain areas except the stratium at 60 min after the injection. PCP also significantly prevented the depletion of 5-HT by PCA in all discrete brain areas except the stratium at 60 min after the injection. From these results, PCP-induced stereotyped behaviors are related to an increased serotonergic neuronal activity due to 5-HT releasing action and/or inhibitory action of 5-HT uptake-by this drug.
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000032:analysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D014364:Tryptophan; D008995:Monoamine Oxidase; D010622:Phencyclidine