Quinpirole (QNP) sensitization is a well-established model of stereotypical checking relevant to obsessive-compulsive disorder. Previously, we found that QNP-treated rats display deficits in hippocampus-dependent tasks. The present study explores the expression of immediate early genes (IEG) during QNP-induced stereotypical checking in the hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC). Adult male rats were injected with QNP (0.5 mg/mL/kg; n = 15) or saline (n = 14) daily for 10 days and exposed to an arena enriched with two objects. Visits to the objects and the corners of the arena were recorded. QNP-treated rats developed an idiosyncratic pattern of visits that persisted across experimental days. On day 11, rats were exposed to the arena twice for 5 min and sacrificed. The expression of IEGs Arc and Homer1a was determined using cellular compartment analysis of temporal activity by fluorescence in situ hybridization. IEG-positive nuclei were counted in the CA1 area of the hippocampus, ACC, OFC, and mPFC. We found significantly fewer IEG-positive nuclei in the CA1 in QNP-treated rats compared to controls. The overlap between IEG expressing neurons was comparable between the groups. We did not observe significant differences in IEG expression between QNP treated and control rats in ACC, OFC, and mPFC. In conclusion, treatment of rats with quinpirole decreases plasticity-related activity in the hippocampus during stereotypical checking.
- MeSH
- antagonisté dopaminu D2 farmakologie MeSH
- chinpyrol farmakologie MeSH
- cingulární gyrus účinky léků fyziologie MeSH
- hipokampus účinky léků fyziologie MeSH
- neurony účinky léků metabolismus MeSH
- neuroplasticita účinky léků fyziologie MeSH
- okamžité časné geny MeSH
- pohybová aktivita účinky léků MeSH
- potkani Long-Evans MeSH
- prefrontální mozková kůra účinky léků fyziologie MeSH
- receptory dopaminu D2 metabolismus MeSH
- receptory dopaminu D3 antagonisté a inhibitory MeSH
- regulace genové exprese účinky léků MeSH
- stereotypní chování účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Možnosti profylaxe CINV (chemotherapy-induced nausea and vomiting) se s příchodem nových antiemetik v posledních dvou desetiletích významně zlepšily. Stále je ale cílem zejména prevence nevolnosti a zvracení, nikoli léčba již vzniklých obtíží. Volba antiemetika závisí na typu nevolnosti a zvracení a emetogenitě protinádorové léčby. Při aplikaci kombinované chemoterapie se emetogenita vyjadřuje nejvíce emetogenním lékem. U vysoce a středně emetogenní chemoterapie je doporučena kombinovaná profylaxe od prvního cyklu chemoterapie. V neposlední řadě je třeba brát v úvahu individuální faktory pacienta a vyhodnocovat efekt profylaxe v předchozích cyklech léčby. Pro dosažení nejlepších výsledků antiemetické terapie a adekvátní profylaxe je nutné postupovat podle aktuálních doporučených postupů.
Over the past two decades major improvements in the management of chemotherapy induced nausea and vomiting (CINV) were obtained. The chemotherapy-induced nausea and vomiting is one of the most frequent side effects in cytostatic therapy and a profound challenge during the therapy of cancer patients. Therefore, standardized guideline-orientated prophylaxis is essential and a fundamental contribution for the success of treatment. Prevention of CINV is an important goal in managing patients with cancer. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors or effect of prior treatment in order to provide adequate prophylaxis. International recommendations focused on antiemetic treatment and prophylaxis are crutial to follow and their implementation in the clinical practice are vital to success.
- MeSH
- antagonisté dopaminu D2 aplikace a dávkování farmakologie MeSH
- antagonisté neurokininových receptorů typu 1 aplikace a dávkování farmakologie MeSH
- antiemetika aplikace a dávkování farmakologie MeSH
- antitumorózní látky aplikace a dávkování škodlivé účinky MeSH
- benzodiazepiny aplikace a dávkování farmakologie MeSH
- chemoprofylaxe MeSH
- glukokortikoidy aplikace a dávkování farmakologie MeSH
- lidé MeSH
- nauzea farmakoterapie chemicky indukované prevence a kontrola MeSH
- serotoninové receptory 5-HT3 - antagonisté aplikace a dávkování farmakologie MeSH
- zvracení * farmakoterapie chemicky indukované prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
AIMS: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. MATERIALS AND METHODS: We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. KEY FINDINGS: We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. SIGNIFICANCE: Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP3R1 activity, which in turn may account for the increase expression of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect.
- MeSH
- antagonisté dopaminu D2 farmakologie MeSH
- antagonisté dopaminu farmakologie MeSH
- buněčné linie MeSH
- haloperidol farmakologie MeSH
- potkani Wistar MeSH
- receptory dopaminu D1 genetika metabolismus MeSH
- receptory dopaminu D2 genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- signální transdukce účinky léků MeSH
- srdce účinky léků MeSH
- srdeční frekvence účinky léků MeSH
- vazba proteinů účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
