title: Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia.
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 [(35)S]GTPγS 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.
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Szűcs
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Büki
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Kékesi
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Horváth
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary. Electronic address: benyhe@brc.hu.
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011869:Radioligand Assay; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D015398:Signal Transduction; D013788:Thalamus / Q000378:metabolism
chemical_list: D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins
keywords: Brain membranes; DAMGO; G-protein stimulation; Opioid receptors; Schizophrenia animal model; [(35)S]GTPγS binding