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

Abstract

We examined whether acute administration of phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor-channel complex, can cause neuronal toxicity that is associated with apoptosis. Three- and 24-month-old 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-matched controls. After observing changes of locomotor activities, the animals were killed 24 h after treatment. The brains were processed for in situ analysis of apoptosis either by propidium iodide (PI) staining, or for the terminal dUTP nick-end labelling (TUNEL) method. The regional distribution of apoptotic nuclei was established using PI staining. Apoptosis was additionally 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 number of neurons exhibiting apoptotic morphology. We found that the total number of apoptotic cells was higher in the brains of 24-month-old rats. Compared 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), and hippocampus (1.4-fold). Accordingly, we concluded that ageing was accompanied by DNA-damage that was most pronounced in the prefrontal cortical neurones. The most prominent elevation in the degree of apoptosis in the young-treated compared to young-untreated rats was detected in the striatum. Comparison of the number of TUNEL-positive cells in treated-aged versus treated-young rats revealed that in all the examined regions of the brain PCP exerted a stronger apoptotic effect in younger animals.