Cerebellar Toxicity of Phencyclidine
The Journal of Neuroscience, March 1995, 75(3): 2097-2108 Cerebellar Toxicity of Phencyclidine Riitta N&kki, Jari Koistinaho, Frank Ft. Sharp, and Stephen M. Sagar Department of Neurology, University of California, and Veterans Affairs Medical Center, San Francisco, California 94121 Phencyclidine (PCP), clizocilpine maleate (MK801), and oth- Phencyclidine (PCP), dizocilpine maleate (MK801), and other er NMDA antagonists are toxic to neurons in the posterior NMDA receptor antagonistshave attracted increasing attention cingulate and retrosplenial cortex. To determine if addition- becauseof their therapeutic potential. These drugs have neuro- al neurons are damaged, the distribution of microglial ac- protective properties in animal studies of focal brain ischemia, tivation and 70 kDa heat shock protein (HSP70) induction where excitotoxicity is proposedto be an important mechanism was studied following the administration of PCP and of neuronal cell death (Dalkara et al., 1990; Martinez-Arizala et MK801 to rats. PCP (10-50 mg/kg) induced microglial ac- al., 1990). Moreover, NMDA antagonists decrease neuronal tivation and neuronal HSP70 mRNA and protein expression damage and dysfunction in other pathological conditions, in- in the posterior cingulate and retrosplenial cortex. In ad- cluding hypoglycemia (Nellgard and Wieloch, 1992) and pro- dition, coronal sections of the cerebellar vermis of PCP (50 longed seizures(Church and Lodge, 1990; Faingold et al., 1993). mg/kg) treated rats contained vertical stripes of activated However, NMDA antagonists are toxic to certain neuronal microglial in the molecular layer. In the sagittal plane, the populations in the brain. Olney et al. (1989) demonstratedthat microglial activation occurred in irregularly shaped patch- the noncompetitive NMDA antagonists,PCP, MK801, and ke- es, suggesting damage to Purkinje cells.
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