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Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia

Szűcs, Edina and Büki, Alexandra and Kékesi, Gabriella and Horváth, Gyöngyi and Benyhe, Sándor (2016) Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia. NEUROSCIENCE LETTERS, 619. pp. 29-33. ISSN 0304-3940

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Abstract

Schizophrenia is a complex mental health disorder. Clinical reports suggest that many patients with schizophrenia are less sensitive to pain than other individuals. Animal models do not interpret schizophrenia completely, but they can model a number of symptoms of the disease, including decreased pain sensitivities and increased pain thresholds of various modalities. Opioid receptors and endogenous opioid peptides have a substantial role in analgesia. In this biochemical study we investigated changes in the signaling properties of the mu-opioid (MOP) receptor in different brain regions, which are involved in the pain transmission, i.e., thalamus, olfactory bulb, prefrontal cortex and hippocampus. Our goal was to compare the transmembrane signaling mediated by MOP receptors in control rats and in a recently developed rat model of schizophrenia. Regulatory G-protein activation via MOP receptors were measured in[35S]GTP gamma S binding assays in the presence of a highly selective MOP receptor peptide agonist, DAMGO. It was found that the MOP receptor mediated activation of G-proteins was substantially lower in membranes prepared from the 'schizophrenic' model rats than in control animals. The potency of DAMGO to activate MOP receptor was also decreased in all brain regions studied. Taken together in our rat model of schizophrenia, MOP receptor mediated G-proteins have a reduced stimulatory activity compared to membrane preparations taken from control animals. The observed distinct changes of opioid receptor functions in different areas of the brain do not explain the augmented nociceptive threshold described in these animals. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: MECHANISMS; MODULATION; PERCEPTION; INHIBITION; ANALGESIA; BINDING; SOCIAL-ISOLATION; PAIN SENSITIVITY; ENDOCANNABINOID SYSTEM; ANIMAL-MODELS; Schizophrenia animal model; DAMGO; OPIOID RECEPTORS; BRAIN MEMBRANES; [S-35]GTP gamma S binding; G-protein stimulation
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 23 Jun 2016 11:58
Last Modified: 23 Jun 2016 11:58
URI: http://real.mtak.hu/id/eprint/36633

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