Determination of hypothalamic neuropeptide levels involved in appetite regulation in atypical antipsychotic drug, risperidone treatment

Kurşungöz, Canan
Although the use of atypical antipsychotic drugs is successful in the treatment of schizophrenia, they cause complications in the long term use that is mainly weight gain. In this study, circulating levels of hypothalamic neuropeptides/hormones, which are related to appetite regulation; neuropeptide Y (NPY), alpha melanocyte stimulating hormone (α-MSH), cocaine and amphethamine regulated transcript (CART) and plus leptin in male schizophrenic patients who were treated with an atypical antipsychotic drug, risperidone, which is a serotonin antagonist, for 4 weeks was investigated. Based on the hypothesis that the risperidone treatment might alter the circulating levels of those neuropeptides through the serotonergic antagonism, it results in the weight gain. Leptin plasma levels were increased in the risperidone treated patients accompanying by weight gain vs controls and NPY, α-MSH, CART levels were decreased in the patients before the treatment but they were not changed after treatment. To determine alterations of those candidate genes mRNA expression levels, male Wistar rats were orally administered with risperidone for 4-weeks. Rat studies show that the mRNA expression and plasma levels of POMC, AgRP, and NPY were decreased but CART mRNA levels were increased while their plasma levels were decreased unexpectedly. In conclusion, the serotonergic antagonism of risperidone on POMC neurons may cause increase in appetite; and hence, increased weight gain and leptin levels, even in a short term trial.


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Kursungoz, Canan; AK, MEHMET; Yanık, Tülin (2015-01-30)
Although the use of atypical antipsychotic drugs has been successful in the treatment of schizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohorrnonal pathways in different brain areas. In this study,...
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The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and ...
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Disruption or malfunctioning of neurotransmitter pathways, especially serotonergic and dopaminergic pathways are closely related to psychotic disorders such as schizophrenia. Antipsychotic medications are becoming widespread; however, in long term treatments, these drugs lead to considerable amount of weight gain as a side effect. Metformin, an antidiabetic drug, has previously been used to treat antipsychotic induced weight gain and aripiprazole has been defined as a neutral antipsychotic drug in terms of ...
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One of the osteoporosis drugs, Raloxifene (Ral) is systemically administrated in high dose at frequent intervals, causing high risk of side effects which influence all the body. As a solution to such issues, delivery systems providing controlled and sustained drug release at therapeutic level from a carrier have been studied recently. The aim of this study was to develop Ral- or Ral-poly(ethylene glycol) (PEG)-loaded poly(ε-caprolactone) (PCL) or PCL:poly(D,L-lactide-co-glycolide) (PLGA) microspheres and to...
Citation Formats
C. Kurşungöz, “Determination of hypothalamic neuropeptide levels involved in appetite regulation in atypical antipsychotic drug, risperidone treatment,” M.S. - Master of Science, Middle East Technical University, 2012.