scholarly journals Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

2015 ◽  
Vol 28 (2) ◽  
pp. 110-116
Author(s):  
Artur Palasz ◽  
Ewa Rojczyk ◽  
Milosz Golyszny ◽  
Lukasz Filipczyk ◽  
John J. Worthington ◽  
...  

ObjectiveThe brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression.MethodsWe assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction.ResultsChronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum.ConclusionsThis stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

2020 ◽  
Vol 47 (10) ◽  
pp. 8273-8278
Author(s):  
Artur Pałasz ◽  
Aneta Piwowarczyk-Nowak ◽  
Aleksandra Suszka-Świtek ◽  
Katarzyna Bogus ◽  
Łukasz Filipczyk ◽  
...  

Abstract Neuropeptides are important, multifunctional regulatory factors of the nervous system, being considered as a novel, atypical sites of antidepressants action. It has already been proven that some of them, such as selective serotonin reuptake inhibitors (SSRI), are able to affect peptidergic pathways in various brain regions. Despite these reports, there is so far no reports regarding the effect of treatment with SSRIs on brain proopiomelanocortin (POMC), kisspeptin, Kiss1R and MCHR1 gene expression. In the current study we examined POMC, kisspeptin, Kiss1R and MCHR1 mRNA expression in the selected brain structures (hypothalamus, hippocampus, amygdala, striatum, cerebellum and brainstem) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR. Long-term treatment with escitalopram led to the upregulation of MCHR1 expression in the rat amygdala. Kisspeptin mRNA level was also increased in the amygdala, but Kiss1R mRNA expressions were elevated in the hippocampus, hypothalamus and cerebellum. POMC mRNA expressions were in turn decreased in the hippocampus, amygdala, cerebellum and brainstem. These results may support the hypothesis that these neuropeptides may be involved in the site-dependent actions of SSRI antidepressants. This is the first report of the effects of escitalopram on POMC, kisspeptin, Kiss1R and MCHR1 in animal brain. Our findings shed a new light on the pharmacology of SSRIs and may contribute to a better understanding of the alternative, neuropeptide-dependent modes of antidepressant action.


Author(s):  
Artur Pałasz ◽  
Piotr Żarczyński ◽  
Katarzyna Bogus ◽  
Kinga Mordecka-Chamera ◽  
Alessandra Della Vecchia ◽  
...  

Abstract Background Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug. Methods Studies were carried out on adult, male Sprague–Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression. Results Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged. Conclusions Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.


2016 ◽  
Vol 26 ◽  
pp. S216
Author(s):  
A. Palasz ◽  
A. Suszka-Świtek ◽  
K. Bogus ◽  
L. Filipczyk ◽  
E. Rojczyk ◽  
...  

2008 ◽  
Vol 301 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Izabela Buraczewska ◽  
Berit Berne ◽  
Magnus Lindberg ◽  
Marie Lodén ◽  
Hans Törmä

2016 ◽  
Vol 174 (5) ◽  
pp. 651-662 ◽  
Author(s):  
Federico Gatto ◽  
Nienke R Biermasz ◽  
Richard A Feelders ◽  
Johan M Kros ◽  
Fadime Dogan ◽  
...  

AbstractObjectiveThe high expression of somatostatin receptor subtype 2 (SSTR2 also known as sst2) usually present in growth hormone (GH)-secreting adenomas is the rationale for therapy with somatostatin analogs (SSAs) in acromegaly. Although SSTR2 expression is a good predictor for biochemical response to SSA treatment, we still face tumors resistant to SSAs despite high SSTR2 expression. Recently, beta-arrestins (β-arrestins) have been highlighted as key players in the regulation of SSTR2 function.DesignTo investigate whether β-arrestins might be useful predictors of responsiveness to long-term SSA treatment in acromegaly, we retrospectively evaluated 35 patients with acromegaly who underwent adenomectomy in two referral centers in The Netherlands.Methodsβ-arrestin mRNA levels were evaluated in adenoma samples, together with SSTR2 (and SSTR5) mRNA and protein expression. Biochemical response to long-term SSA treatment (median 12 months) was assessed in 32 patients.Resultsβ-arrestin 1 and 2 mRNA was significantly lower in adenoma tissues from patients who achieved insulin-like growth factor 1 normalization (P= 0.024 andP= 0.047) and complete biochemical control (P= 0.047 andP= 0.039). The SSTR2 mRNA was higher in SSA responder patients compared with the resistant ones (P= 0.026). This difference was more evident when analyzing the SSTR2/β-arrestin 1 and SSTR2/β-arrestin 2 ratio (P= 0.011 andP= 0.010). β-arrestin 1 and 2 expression showed a significant trend of higher median values from full responders, partial responders to resistant patients (P= 0.045 andP= 0.021, respectively). Interestingly, SSTR2 protein expression showed a strong inverse correlation with both β-arrestin 1 and 2 mRNA (ρ= –0.69,P= 0.0011 andρ= –0.67,P= 0.0016).ConclusionsLow β-arrestin expression and high SSTR2/β-arrestin ratio correlate with the responsiveness to long-term treatment with SSAs in patients with acromegaly.


Author(s):  
Katarzyna Bogus ◽  
Małgorzata Żarczyńska ◽  
Artur Pałasz ◽  
Aleksandra Suszka-Świtek ◽  
John J. Worthington ◽  
...  

Abstract Background Neurosteroids are involved in several important brain functions and have recently been considered novel players in the mechanic actions of neuropsychiatric drugs. There are no reports of murine studies focusing on the effect of chronic neurosteroid treatment in parallel with antipsychotics on key steroidogenic enzyme expression and we therefore focused on steroidogenic enzyme gene expression in the brainstem of rats chronically treated with olanzapine and haloperidol. Methods and results Studies were carried out on adult, male Sprague–Dawley rats which were divided into 3 groups: control and experimental animals treated with olanzapine or haloperidol. Total mRNA was isolated from homogenized brainstem samples for RealTime-PCR to estimate gene expression of related aromatase, 3β-HSD and P450scc. Long-term treatment with the selected antipsychotics was reflected in the modulation of steroidogenic enzyme gene expression in the examined brainstem region; with both olanzapine and haloperidol increasing aromatase, 3β-HSD and P450scc gene expression. Conclusions The present findings shed new light on the pharmacology of antipsychotics and suggest the existence of possible regulatory interplay between neuroleptic action and steroidogenesis at the level of brainstem neuronal centres.


2001 ◽  
Vol 120 (5) ◽  
pp. A115-A115 ◽  
Author(s):  
E CALVERT ◽  
L HOUGHTON ◽  
P COOPER ◽  
P WHORWELL

2004 ◽  
Vol 171 (4S) ◽  
pp. 424-424 ◽  
Author(s):  
Monica G. Ferrini ◽  
Eliane G. Valente ◽  
Jacob Rajfer ◽  
Nestor F. Gonzalez-Cadavid

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