Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
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PMID:Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats. 282 56

The possible involvement of the serotonergic neuronal system in aversive motivation produced by phencyclidine [1-(1-phenylcyclohexyl)piperidine; PCP] was investigated using a place-conditioning paradigm in rats. PCP (4 mg/kg, i.p.) produced place aversion in this task as reported previously (Kitaichi K, Noda Y, Hasegawa T, Furukawa H, Nabeshima T. Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats. Eur J Pharmacol 1996;318:7-9). The blockade of serotonin2A (5-HT2A) receptors using the antagonist ritanserin (3 and 10 mg/kg, p.o.) significantly attenuated this aversive property of PCP whereas lesions of serotonergic neurons using 5,7-dihydroxytryptamine (5,7-DHT, 100 microg/animal, i.c.v.) failed to affect it. Repeated PCP treatment (10 mg/kg, i.p. for 14 days), which is enough to diminish the stereotyped 5-HT2A receptor-mediated head-twitch behavior, also decreased the place aversion. These results suggest that the serotonergic neuronal system, specifically the 5-HT2A receptor, may play a critical role in producing PCP-induced place aversion.
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PMID:Involvement of the serotonergic neuronal system in phencyclidine-induced place aversion in rats. 1047 70

Antagonism of N-methyl-D-aspartate (NMDA) receptors by phencyclidine (PCP) is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of PCP, without changing the action of the more selective NMDA receptor antagonist, MK-801. Here we compared locomotor responses to PCP and MK-801 in rats that were administered 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or ventral hippocampus, which are preferentially innervated by median and dorsal raphe, respectively. Dorsal hippocampus lesions potentiated PCP-induced hyperlocomotion (0.5, 2.5 mg/kg), but not the effect of MK-801 (0.1 mg/kg). Ventral hippocampus lesions did not alter the hyperlocomotion elicited by either compound. Given that PCP and MK-801 may induce different spatiotemporal patterns of locomotor behavior, together with the known role of the dorsal hippocampus in spatial processing, we also assessed whether the 5,7-DHT-lesions caused any qualitative differences in locomotor responses. Treatment with PCP or MK-801 increased the smoothness of the path traveled (reduced spatial d) and decreased the predictability of locomotor patterns within the chambers (increased entropy). 5,7-DHT-lesions of the dorsal hippocampus did not alter the effects of PCP on spatial d or entropy - despite potentiating total distance moved - but caused a slight reduction in levels of MK-801-induced entropy. Taken together, serotonergic lesions targeting the dorsal hippocampus unmask a functional differentiation of the hyperlocomotor effects of PCP and MK-801. These findings have implications for studies utilizing NMDA receptor antagonists in modeling glutamatergic dysfunction in schizophrenia.
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PMID:Hippocampal serotonin depletion unmasks differences in the hyperlocomotor effects of phencyclidine and MK-801: quantitative versus qualitative analyses. 2400 84