Effects of haloperidol on striatal neurons: relation to neuronal loss (a stereological study)

Abstract

In the present work, we investigated the effect of chronic haloperidol administration on the number of striatal neurons in guinea pigs. For this purpose, adult male guinea pigs were given daily injections of 1, 2 or 3 mg/kg of haloperidol for 6 weeks. After treatment, the animals were anesthetized via brief inhalation of ether, the brains were removed and the corpus striatum was dissected. Then the tissues were processed and semi-thin sections were stained with toluidine blue for stereological and histopathological evaluation. The physical disector was used for measurements of nuclear height and numerical density of striatal neurons and also to evaluate both normal and degenerated neurons within the corpus striatum of treated animals and untreated controls. In the control group, the mean numerical density of neurons was calculated as 47.92 cell/mm(3) and the mean nuclear height as 3.58 mu m. Mean densities of all (both viable and degenerated) neurons were calculated to be 45.46 in the low-dose (p < 0.01), 39.73 in the medium-dose (p < 0.001) and 30.31 cell/mm(3) in the high-dose group (p < 0.001). Mean densities of degenerated neurons in the low, medium and high dose group were 30.72, 22.93 (p < 0.001) and 15.56 cell/mm(3) (p < 0.001) respectively Mean nuclear heights were 2.804 (p < 0.0001), 2.78 (p < 0.0001) and 2.33 mu m (p < 0.00001) in the low, medium and high dose group, respectively. These results suggest that haloperidol treatment may lead to loss of neurons and decrease in the nuclear size within the corpus striatum.