ArticleBMC pharmacology & toxicology2017
Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine.
Article in BMC pharmacology & toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?Psychopharmacology · 2021Trial
- Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.Biomedicines · 2024Review
- Article
- Maternal immune activation affects female offspring whisker movements during object exploration in a rat model of neurodevelopmental disorders.Brain, behavior, & immunity - health · 2024Article
- Selective 5-HTPharmaceuticals (Basel, Switzerland) · 2023Article
- Subacute toxic effects of silver nanoparticles oral administration and withdrawal on the structure and function of adult Albino Rats' hepatic tissue.Saudi journal of biological sciences · 2022Article
- Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics.Frontiers in endocrinology · 2020Review
- Long-term Use of Clozapine is Protective for Bone Density in Patients with Schizophrenia.Scientific reports · 2019Article
- Effects of clozapine and haloperidol treatment on plasma concentrations of androgen hormones and androgendependent organ changes in rats.Indian journal of pharmacologyArticle
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe presentation of schizophrenia (SCH) symptoms differs between the sexes. Long-term treatment with antipsychotics is frequently associated with decreased bone mineral density, increased fracture risk and metabolic side effects. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, body composition, corticosterone, IL-6 and TNF-α concentrations and metabolic parameters in male and female rats perinatally treated with PCP.
methodsSix groups of male and six groups of female rats (n = 6-12 per group) were subcutaneously treated on 2nd, 6th, 9th and 12th postnatal day (PN), with either PCP (10 mg/kg) or saline. At PN35, one NaCl and PCP group (NaCl-H and PCP-H) started receiving haloperidol (1 mg/kg/day) and one NaCl and PCP group (NaCl-C and PCP-C) started receiving clozapine (20 mg/kg/day) dissolved in drinking water. The remaining NaCl and PCP groups received water. Dual X-ray absorptiometry measurements were performed on PN60 and PN98. Animals were sacrificed on PN100. Femur was analysed by light microscopy. Concentrations of corticosterone, TNF-α and IL-6 were measured in serum samples using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Glucose, cholesterol and triacylglycerol concentrations were measured in serum spectrophotometrically.
resultsOur results showed that perinatal PCP administration causes a significant decrease in bone mass and deterioration in bone quality in male and female rats. Haloperidol had deleterious, while clozapine had protective effect on bones. The effects of haloperidol on bones were more pronounced in male rats. It seems that the observed changes are not the consequence of the alterations of corticosterone, IL-6 and TNF-α concentration since no change of these factors was observed. Clozapine induced increase of body weight and retroperitoneal fat in male rats regardless of perinatal treatment. Furthermore, clozapine treatment caused sex specific increase in pro-inflammatory cytokines.
conclusionTaken together our findings confirm that antipsychotics have complex influence on bone and metabolism. Evaluation of potential markers for individual risk of antipsychotics induced adverse effects could be valuable for improvement of therapy of this life-long lasting disease.
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