Atypical anti-schizophrenic drugs prevent changes in cortical N-methyl- d-aspartate receptors and behavior following sub-chronic phencyclidine administration in developing rat pups

• Published in: Pharmacology, biochemistry and behavior Vol. 90; no. 4; pp. 569 - 577
• Main Authors: Anastasio, Noelle C., Johnson, Kenneth M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2008; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Animals; Antipsychotic Agents - pharmacology; Behavior, Animal - drug effects; Behavioral sensitization; Biological and medical sciences; Blotting, Western; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Down-Regulation - drug effects; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Female; Locomotor activity; Male; Medical sciences; Motor Activity - drug effects; Neostriatum - drug effects; Neostriatum - metabolism; NMDA receptor; Olanzapine; Phencyclidine; Phencyclidine - administration & dosage; Phencyclidine - antagonists & inhibitors; Phencyclidine - pharmacology; Pre-pulse inhibition; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - drug effects; Reflex, Startle - drug effects; Risperidone; Schizophrenia; Schizophrenia - drug therapy; Subcellular Fractions - drug effects; Phencyclidine; Olanzapine; Pre-pulse inhibition; Behavioral sensitization; NMDA receptor; Risperidone; Locomotor activity; Drug; Subchronic; Rat; Psychotropic; Rodentia; Phencyclidine;NMDA receptor;Olanzapine;Risperidone;Pre-pulse inhibition;Locomotor activity;Behavioral sensitization; Schizophrenia; Glutamate receptor; Neuroprotective agent; Psychosis; Vertebrata; Mammalia; Animal; Piperidine derivatives; Hallucinogen; Development; Sensitization; Drug of abuse; Antagonist; Behavior
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2008.04.017

We sought to determine the relationship between phencyclidine (PCP)-induced alterations in behavior and NMDAR expression in the cortex by examining the effect of anti-schizophrenic drug treatment on both. Sprague–Dawley rat pups were pretreated with risperidone or olanzapine prior to treatment with PCP on postnatal day 7 (PN7) or sub-chronically on PN7, 9, and 11. Pre-pulse inhibition (PPI) of acoustic startle was measured on PN24–26 and following a challenge dose of 4 mg/kg PCP, locomotor activity was measured on PN28–35. PCP treatment on PN7 did not cause a deficit in PPI, but did cause locomotor sensitization. This was prevented by both antipsychotics. PCP treatment on PN7 caused an up-regulation of NR1 and NR2B, which was not affected by either anti-schizophrenic drug. PCP treatment on PN7, 9, and 11 caused a deficit in PPI and a sensitized locomotor response to PCP challenge as well as an up-regulation of NR1 and NR2A, all of which were prevented by both atypical anti-schizophrenic drugs. These data support the hypothesis that sub-chronic, but not single injection PCP treatment in developing rats results in behavioral alterations that are sensitive to antipsychotic drugs and these behavioral changes observed could be related to up-regulation of cortical NR1/NR2A receptors.