Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). Aim of this work was to investigate possible changes in IP3Rs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IP3Rs (IP3R1s) and σ1Rs at mRNA and protein levels. Haloperidol treatment did not alter expression of other types of IP3Rs. Calcium release from endoplasmic reticulum (ER) mediated by increased amount of IP3R1s elevated cytosolic calcium and generated ER stress. IP3R1s were bound to σ1Rs, and translocation of this complex from ER to nucleus occurred in the group of cells treated with haloperidol, which was followed by increased nuclear calcium levels. Haloperidol-induced changes in cytosolic, reticular, and nuclear calcium levels were similar when specific σ1 blocker -BD 1047- was used. Changes in calcium levels in nucleus, ER, and cytoplasm might be responsible for alterations in cellular plasticity, because length of neurites increased and number of neurites decreased in haloperidol-treated differentiated NG-108 cells.

• Keywords
• BD 1047, Dopamine 2 receptor, Haloperidol, Inositol 1,4,5-trisphosphate receptor, NG-108 cells, Sigma 1 receptor,
• MeSH
• Antipsychotic Agents pharmacology   MeSH
• Cell Differentiation drug effects   physiology   MeSH
• Haloperidol pharmacology   MeSH
• Inositol 1,4,5-Trisphosphate Receptors metabolism   MeSH
• Rats MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Neuronal Plasticity drug effects   physiology   MeSH
• Sigma-1 Receptor MeSH
• Receptors, sigma metabolism   MeSH
• Protein Binding drug effects   physiology   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antipsychotic Agents MeSH
• Haloperidol MeSH
• Inositol 1,4,5-Trisphosphate Receptors MeSH
• Itpr1 protein, rat MeSH Browser
• Receptors, sigma MeSH