| Treatment with the N-methyl-D-aspartate receptor antagonists ketamine (KET) or phencyclidine (PCP) can trigger apoptotic neurodegeneration in neonatal rodents; however, little is known about the behavioral alterations resulting from such neurodegeneration. Here, rats were sc treated with: saline; 10 mg/kg PCP (1x/day) on postnatal days (PNDs) 7, 9 and 11; 20 mg/kg KET (6 injections every 2 hours on PND 7); or a similar regimen of ketamine and 250 mg/kg L-carnitine (LC) on PND 7, with a single injection of 250 mg/kg LC on PNDs 8-11 (KLC). Post-injection, home cage behavior of each pup was categorized on PNDs 7-11. Slant board (PNDs 8-11), forelimb hang (PNDs 12-16), prepulse inhibition (PPI; PND 25), grip strength and motor coordination (PND 22 or 71), locomotor sensitization (PND 42), spatial alternation (PNDs 22-70) and residential running wheel activity (PNDs 72-77) were also examined. The initial KET or KLC treatments on PND 7 elevated abnormal home cage activity; however, behavior of KLC-treated pups returned to control levels more quickly than that of the KET-treated pups, indicating the protective effects of LC. PCP treatment caused substantial abnormal home cage activity on each treatment day (PND 7, 9, and 11). Latencies to turn on the slant board on PND 8 were significantly longer for KET- and PCP-treated pups and on PND 10 for PCP-treated pups. On PND 12, the forelimb hang time of PCP-treated pups was significantly shorter. Despite the magnitude of PCP-induced preweaning changes, PPI behaviors of PCP-, KET-, and KLC-treated groups were comparable to controls. Developmentally treated KET- or KLC-treated rats responded to a 5 mg/kg KET challenge with activity similar to controls which received the same challenge. However, developmental PCP treatment induced significant sensitization to a 3 mg/kg PCP challenge relative to controls which received the same challenge, causing substantially increased open field activity. Performance on a spatial alternation task was unaffected by neonatal KET, KLC or PCP treatment; however, neonatal PCP treatment elevated light and dark period running wheel activity. These data indicate that developmental PCP treatment causes short- and long-term behavioral alterations and suggest that neonatal KET treatment does not result in lasting behavioral modifications. |
