Nov 14, 2006

Typical and atypical antipsychotic drug effects on locomotor hyperactivity and deficits in sensorimotor gating in a genetic model of NMDA receptor hypofunction

Pharmacology, Biochemistry, and Behavior
Gary E DuncanBeverly H Koller


Psychotomimetic effects of NMDA antagonists in humans suggest that NMDA receptor hypofunction could contribute to the pathophysiology of schizophrenia. A mouse line that expresses low levels of the NMDA R1 subunit (NR1) of the NMDA receptor was generated to model endogenous NMDA hypofunction. These mutant mice show increased locomotor activity, increased acoustic startle reactivity and deficits in prepulse inhibition (PPI) of acoustic startle. The present study examined effects of a typical antipsychotic drug, haloperidol, and two atypical antipsychotic drugs (olanzapine and risperidone) on behavioral alterations in the NR1 hypomorphic (NR1-/-) mice. Haloperidol significantly reduced activity in the wild type controls at each dose tested (0.05, 0.1, and 0.2 mg/kg). The NR1-/- mice were less sensitive to the haloperidol-induced locomotor inhibition in comparison to the NR1+/+ mice. In contrast to haloperidol, olanzapine reduced the hyperactivity in the NR1-/- mice at a dose that produced minimal effects on locomotor activity in the wild type mice. These data suggest that non-dopaminergic blocking properties of olanzapine contribute to the drug's ability to reduce hyperactivity in the NR1 deficient mice. In the PPI paradigm, halo...Continue Reading

  • References39
  • Citations41


Mentioned in this Paper

Metabolic Process, Cellular
Neuro-Oncological Ventral Antigen 2
Antipsychotic Effect
Atypical Antipsychotic [EPC]
Adrenal Cortex Diseases
Assay OF Haloperidol
C57BL/6 Mouse

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