RESUMEN
Previous pharmacological data have shown the possible existence of functional interactions between µ- (MOP), κ- (KOP), and δ-opioid receptors (DOP) in pain and mood disorders. We previously reported that MOP knockout (KO) mice exhibit a lower stress response compared with wildtype (WT) mice. Moreover, DOP agonists have been shown to exert antidepressant-like effects in numerous animal models. In the present study, the tail suspension test (TST) and forced swim test (FST) were used to examine the roles of MOP and DOP in behavioral despair. MOP-KO mice and WT mice were treated with KNT-127 (10 mg/kg), a selective DOP agonist. The results indicated a significant decrease in immobility time in the KNT-127 group compared with the saline group in all genotypes in both tests. In the saline groups, immobility time significantly decreased in MOP-KO mice compared with WT mice in both tests. In female MOP-KO mice, KNT-127 significantly decreased immobility time in the TST compared with WT mice. In male MOP-KO mice, however, no genotypic differences were found in the TST after either KNT-127 or saline treatment. Thus, at least in the FST and TST, the activation of DOP and absence of MOP had additive effects in reducing measures of behavioral despair, suggesting that effects on this behavior by DOP activation occur independently of MOP.
Asunto(s)
Morfinanos , Receptores Opioides mu , Masculino , Femenino , Ratones , Animales , Morfinanos/farmacología , Antidepresivos/farmacología , Analgésicos Opioides/farmacología , Dolor/tratamiento farmacológicoRESUMEN
Rubiscolin6 is a foodderived opioid peptide found in Spinacia oleracea that has antinociceptive, memoryenhancing, anxiolyticlike and antidepressant effects. Rubiscolin6 has been reported to have two opposing effects on food intake. Food intake is closely connected to gut motility; however, to the best of our knowledge, the effect of rubiscolin6 on gut motility has not been reported. The present study aimed to investigate the effect of rubiscolin6 on postprandial motility of the gastric antrum in conscious mice. A catheter was implanted in the gastric antrum of male C57BL/6J mice. Manometric measurements were performed in fasted male mice and chow was then provided to assess motility in the fed state. Rubiscolin6, the δopioid receptor antagonist naltrindole, a mixture of rubiscolin6 and naltrindole, or vehicle was administered intraperitoneally 30 min after eating. The percentage motor index (%MI) was then calculated. Cumulative food intake was measured in both ad libitumfed and overnightfasted mice. The %MI was significantly lower in mice treated with rubiscolin6 compared with that in the other groups, but normalized by treatment with the rubiscolin6/naltrindole mixture. The decrease in %MI induced by rubiscolin6 remained for 1 h after administration. Cumulative food intake was significantly higher 4 and 6 h after rubiscolin6 administration in ad libitumfed mice but was normalized by the rubiscolin6/naltrindole mixture. Food intake 30 min after rubiscolin6 administration was normal, but was higher in mice treated with the rubiscolin6/naltrindole mixture. Thus, rubiscolin6 may have a rapid effect to reduce postprandial antral motility and may subsequently increase food intake after this inhibitory effect disappears. These effects were revealed to be mediated through δopioid receptors. The orexigenic effect of rubiscolin6 may be applicable to the treatment of anorexia and cachexia.
Asunto(s)
Ansiolíticos , Antro Pilórico , Animales , Ansiolíticos/farmacología , Ingestión de Alimentos , Masculino , Ratones , Ratones Endogámicos C57BL , Antagonistas de Narcóticos/farmacología , Péptidos Opioides/farmacología , Fragmentos de Péptidos , Receptores Opioides , Ribulosa-Bifosfato CarboxilasaRESUMEN
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry staining were applied for the expressions of Bad, Bax, Bcl-2 and cleaved caspase-3. The MCAO group showed higher CI volume, nerve cell apoptosis and cleaved caspase-3 expressions than the DADLE and DMSO groups, which were also higher in the LY294002 group than the DADLE group. Compared with the MCAO group, the mRNA and protein expressions of PI3K and Bcl-2, and the protein expressions of p-Akt and p-Bad were elevated, while the mRNA and protein expressions of Bax were decreased in the DADLE and DMSO groups. Decreased mRNA and protein expressions of PI3K and Bcl-2, reduced protein expressions of p-Akt and p-Bad and elevated mRNA and protein expressions of Bax exhibited in the LY294002 group than the DADLE group. These results indicate that activation of PI3K-Akt pathway promotes the neuroprotection of DADLE against cerebral I/R injury in a rat model by decreasing nerve cells apoptosis.