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

Repeated treatment with phencyclidine (PCP) prolonged the immobility time in a forced swimming test, compared with saline treatment, this behavioral change being regarded as avolition which is one of the negative symptoms of schizophrenia. In the present study, we investigated an involvement of serotonergic (5-HTergic) and dopaminergic systems in PCP-induced enhancement of immobility in mice, since an alteration in 5-HTergic and dopaminergic systems has been hypothesized in schizophrenia. The enhancing effect of PCP on the immobility in a forced swimming test was attenuated by clozapine, risperidone and olanzapine, which have serotonin (5-HT) and dopamine receptor antagonistic properties. These attenuating effects were significantly antagonized by a 5-HT(2) receptor agonist, (+/-)-2,5-dimethoxy-4-iodamphetamine (DOI) without affecting the immobility itself. (-)Sulpiride at a low dose and methylphenidate reversed the PCP-induced enhancement of immobility whereas pimozide, chlorpromazine and levomepromazine had no effect. There was no difference in the frequency of DOI-induced head twitches, which are mediated via 5-HT(2) receptors, between PCP- and saline-treated mice following the forced swimming test, indicating no functional changes in post-synaptic 5-HT(2) receptors. 5-HT utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in mice showing PCP-induced enhancement of immobility. These results suggest that the enhanced effect of PCP on the immobility is mediated by imbalance of 5-HTergic and dopaminergic systems in the prefrontal cortex and could be used as a model of the negative symptoms of schizophrenia.
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PMID:Repeated phencyclidine treatment induces negative symptom-like behavior in forced swimming test in mice: imbalance of prefrontal serotonergic and dopaminergic functions. 1098 64

The role of 5-hydroxytryptamine (serotonin) (5-HT)(7) receptor antagonism in the actions of atypical antipsychotic drugs (APDs), e.g., amisulpride, clozapine, and lurasidone, if any, is uncertain. We examined the ability of 5-HT(7) receptor antagonism alone and as a component of amisulpride and lurasidone to reverse deficits in rat novel object recognition (NOR) produced by subchronic treatment with the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP), and we examined the ability of supplemental 5-HT(7) antagonism to augment the inability of sulpiride, haloperidol, and (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), a metabotropic glutamate receptor (mGluR) 2/3 agonist, which lack 5-HT(7) antagonism, to reverse the NOR deficit. The 5-HT(7) receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970) (0.1-1 mg/kg) dose-dependently reversed PCP-induced NOR deficits. In addition, the ability of lurasidone (0.1 mg/kg) and amisulpride (3 mg/kg) to reverse this deficit was blocked by cotreatment with the 5-HT(7) receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS19) (5-10 mg/kg), which did not affect NOR in naive rats. Sulpiride, a less potent 5-HT(7) antagonist than amisulpride, did not itself improve the PCP-induced NOR deficit. However, a subeffective dose of SB269970 (0.1 mg/kg) in combination with subeffective doses of lurasidone (0.03 mg/kg), amisulpride (1 mg/kg), or sulpiride (20 mg/kg), also reversed the PCP-induced NOR deficit. Pimavanserin, a 5-HT(2A) inverse agonist, LY379268, and haloperidol did not potentiate the ability of subeffective SB269970 to improve the NOR deficit. Furthermore, the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), which blocks the effect of clozapine to reverse the NOR deficit, did not block the SB269970-induced amelioration of the NOR deficit. These results suggest 5-HT(7) antagonism may contribute to the efficacy of some atypical APDs in the treatment of cognitive impairment in schizophrenia and may itself have some benefit in this regard.
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PMID:The role of 5-hydroxytryptamine 7 receptors in the phencyclidine-induced novel object recognition deficit in rats. 2155 35