THE ROLE OF NMDA AND SIGMA-SYSTEMS IN THE BEHAVIORAL-EFFECTS OF PHENCYCLIDINE IN PREWEANLING RATS

To determine the role of NMDA receptor blockade and sigma receptors in the behavioral effects of PCP during development, we assessed the beh avioral effects of PCP, (+)-MK-801 and 1,3-Di(2-tolyl)guanidine (DTG) in preweanling rats. In the first experiment, rats were injected sc on postnatal day (PND) 19 with 0.5 - 4.5 mg/kg PCP, and locomotor activi ty and wall climbing behavior were scored. PCP induced high levels of locomotor activity on PND 19 in a dose dependent manner with the 2.0 m g/kg dose producing the greatest activity. In the second experiment, r ats were injected on PND 12 or 19 with 1.0 - 4.0 mg/kg PCP or 0.1 - 0. 4 mg/kg (+)-MK-801 and tested using the same procedures. Both PCP and (+)-MK-801 induced activity increases on PND 19 in a dose dependent ma nner, with 2.0 and 3.0 mg/kg PCP and 0.2 mg/ kg (+)-MK-801 inducing th e highest activity levels. Peak activity levels on PND 12 were approxi mately 30% of those observed on PND 19, with the lowest dose of PCP an d (+)-MK-801 producing the greatest activity. Large amounts of wall cl imbing behavior were elicited by PCP on PND 12, whereas (+)-MK-801 ind uced only minor amounts of wall climbing. In the third experiment, the effects of 0, 1, 3, 6, or 12 mg/kg DTG were examined in PND 13-14 and 16-77 rats. DTG had little effect on locomotor activity on PND 13-14, although the highest dose did inhibit activity. On PND 16-17, all dos es of DTG tended to increase locomotor activity. The results suggest ( 1) the robust locomotor effects of PCP on PND 19 are mediated in part by NMDA mechanisms (2) this period of increased sensitivity to both PC P and (+)-MK-801 might represent a critical period of development when systems mediating locomotor activity are vulnerable to neurotoxic ins ult (3) NMDA blockade alone does not mediate PCP-induced wall climbing behavior and (4) that at the doses of DTG and the ages tested, sigma receptors do not play a role in the locomotor-inducing effects of PCP. (C) 1994 Intox Press, Inc.