Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study.
In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications.
Departments of Histology and Embryology, Medical Faculty of Atatürk University, Erzurum, Turkey.
B Zuhal
BZ
Altunkaynak
Elvan
E
Ozbek
Bunyami
B
Unal
Nazan
N
Aydin
M Dumlu
MD
Aydin
Ozgen
O
Vuraler
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006220:Haloperidol / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008853:Microscopy / Q000379:methods; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats
D014150:Antipsychotic Agents; D006220:Haloperidol