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)

Treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptotic neurodegeneration in neonatal rodents; however, little is known about the behavioral alterations resulting from such treatment. Here, rats were sc treated with saline; 10 mg/kg PCP on postnatal days (PNDs) 7, 9, and 11; 20 mg/kg KET (six injections every 2 h on PND 7); or a regimen of ketamine and 250 mg/kg L-carnitine (KLC) both administered on PND 7 with additional 250 mg/kg doses of L-carnitine given on PNDs 8-11. Postinjection, the home cage behavior of each pup was categorized on PNDs 7-11. Slant board and forelimb hang behaviors were examined on PNDs 8-11 and 12-16, respectively. The initial KET or KLC injections on PND 7 elevated abnormal home cage activity (i.e., paresis and paddling); however, KLC pup behavior returned to normal by the fourth injection, indicating the protective effects of L-carnitine against NMDA antagonist toxicity. PCP treatment caused substantial abnormal home cage activity on each injection day (PNDs 7, 9, and 11). Latencies to turn on the slant board were significantly longer on PND 8 for KET- and PCP-treated pups and PND 10 for PCP-treated pups. On PND 12, the forelimb hang time of PCP-treated pups was significantly shorter. Body weight was decreased on PNDs 8-18 in PCP-treated pups and PNDs 8-10 in KET-treated pups. These data indicate that developmental NMDA antagonist treatment causes short-term behavioral alterations which appear related to motor coordination and may be cerebellar in nature. Furthermore, single PCP injections appear more potent at altering behavior than multiple injections of KET.
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PMID:Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats. 1866 23

Glutamate activation of the NMDA receptor is essential for neuronal differentiation, migration, and survival. Treatment with NMDA receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptosis in neonatal rats. However, L-carnitine (LC) treatment appears to prevent glutamate-induced toxicity in the developing CNS. Previously, we described altered preweaning behaviors (i.e., abnormal home cage, slant board and forelimb hang behaviors) resulting from neonatal PCP and KET treatment. Those adverse effects of KET were somewhat ameliorated by LC [Boctor SY, Wang C, Ferguson SA. Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats. Toxicol Sci 2008;106:172-9]. Here, a portion of those subjects were evaluated for prepulse inhibition (PPI) of the acoustic startle response at postnatal day (PND) 25 since previous reports described PCP-induced effects on this response. Rats were subcutaneously treated with: saline; 10 mg/kg PCP (1x/day) on PNDs 7, 9 and 11; 20 mg/kg KET (6 injections every 2h on PND 7); or a similar regimen of ketamine and 250 mg/kg LC on PND 7, with a single injection of 250 mg/kg LC on PNDs 8-11 (KLC). Male and female rats were assessed using a standard PPI paradigm with prepulses of 68, 78 and 82 dB. Body weight was decreased 17-21% and whole brain weight was decreased 10% in PCP-treated rats. Specifically, cerebellar weight was significantly less in PCP-treated rats relative to control. Despite the magnitude of those PCP-induced changes, startle response in normal pulse only trials and percent of PPI in PCP-, KET-, and KLC-treated groups were comparable to controls. Average latency to maximum startle was 2.6 ms less in females than males (p<0.007); there were no other significant sex effects. The lack of neonatal PCP treatment on later PPI is similar to that reported by Rasmussen et al. [Rasmussen BA, O'Neil J, Manaye KF, Perry DC, Tizabi Y. Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats. Psychopharmacology (Berl) 2007; 190: 43-9.], and indicates that neonatal PCP-induced effects on PPI [Wang C, McInnis J, Ross-Sanchez M, Shinnick-Gallagher P, Wiley JL, Johnson KM. Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 2001; 107: 535-50.] appear difficult to replicate.
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PMID:Neonatal NMDA receptor antagonist treatments have no effects on prepulse inhibition of postnatal day 25 Sprague-Dawley rats. 1903 86

Neonatal ketamine (KET) or phencyclidine (PCP) treatment can trigger apoptotic neurodegeneration in rodents. Previously, we described KET- and PCP-induced altered body weight and home cage, slant board and forelimb hang behaviors in preweaning rats (Boctor et al., 2008). In that study, L-carnitine (LC) attenuated the KET-induced behavioral alterations and body weight decrements. The four subcutaneous (sc) treatment groups were: (1) saline; (2) 10 mg/kg PCP on PNDs 7, 9 and 11; (3) 20 mg/kg KET (6 injections; one every 2h on PND 7); or (4) a regimen of KET and 250 mg/kg LC (KLC) both administered on PND 7, with additional 250 mg/kg doses of LC on PNDs 8-11. A portion of each treatment group was evaluated for postweaning behaviors which included grip strength and motor coordination (postnatal days (PNDs) 22 or 71), locomotor sensitization (PND 42), spatial alternation (PNDs 22-70) and residential running wheel activity (PNDs 72-77). On PND 42 or 78, whole and regional brain weights were measured. Grip strength and motor coordination were unaffected at either age by neonatal treatment. On PND 42, neonatally treated KET- or KLC-treated rats responded to a challenge of 5mg/kg KET with activity similar to controls that received the same challenge. Neonatal PCP treatment, however, induced significant sensitization to a challenge of 3mg/kg PCP on PND 42 relative to controls that received the same challenge, causing increased activity which was especially profound in females. Performance on a continuous spatial alternation task requiring a "win-shift, lose-stay" strategy appeared unaffected by neonatal KET or KLC treatment. PCP treatment, however, caused significantly increased random responding and shorter choice latencies. In addition, neonatal PCP treatment elevated light and dark period running wheel activity and reduced PND 42 and 78 body and whole brain weights. These findings provide further evidence that PCP treatment on PNDs 7, 9, and 11 causes subtle cognitive deficits and long-term alterations in activity that are unrelated to deficits in grip strength or motor coordination. Further, repeated KET treatment on PND 7 does not appear to result in severe behavioral modifications.
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PMID:Altered adult locomotor activity in rats from phencyclidine treatment on postnatal days 7, 9 and 11, but not repeated ketamine treatment on postnatal day 7. 1985 22