Apoptosis induction by phencyclidine in the brains of rats of different ages

We examined whether acute administration of phencyclidine (PCP), an antagon ist of the N-methyl-D-aspartate (NMDA) receptor-channel complex, can cause neuronal toxicity that is associated with apoptosis. Three- and 24-month-ol d rats were placed in locomotor activity chambers. PCP (50 mg/kg) or saline (0.15 M NaCl) were simultaneously administered to the treated and age-matc hed controls. After observing changes of locomotor activities, the animals were killed 24 h after treatment. The brains were processed for in situ ana lysis of apoptosis either by propidium iodide (PI) staining, or for the ter minal dUTP nick-end labelling (TUNEL) method. The regional distribution of apoptotic nuclei was established using PI staining. Apoptosis was additiona lly confirmed and quantified by the TUNEL technique. PI and TUNEL staining revealed that PCP-mediated neurotoxicity in the prefrontal and enthorhinal cortices, the striatum and hippocampus was associated with a significant nu mber of neurons exhibiting apoptotic morphology. We found that the total nu mber of apoptotic cells was higher in the brains of 24-month-old rats. Comp ared to the respective controls the number of apoptotic cells was 3.8-fold greater in the cortex of old rats, followed by the striatum (three-fold), a nd hippocampus (1.4-fold). Accordingly, we concluded that ageing was accomp anied by DNA-damage that was most pronounced in the prefrontal cortical neu rones. The most prominent elevation in the degree of apoptosis in the young -treated compared to young-untreated rats was detected in the striatum. Com parison of the number of TUNEL-positive cells in treated-aged versus treate d-young rats revealed that in all the examined regions of the brain PCP exe rted a stronger apoptotic effect in younger animals.