RESUMO
RATIONALE: Recently, we demonstrated that the activation of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) signaling facilitates depressive-like behaviors. Additionally, literature findings support the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal (HPA) axis. OBJECTIVES: Considering that dysfunctional HPA axis is strictly related to stress-induced psychopathologies, we aimed to study the role of the HPA axis in the pro-depressant effects of NOP agonists. METHODS: Mice were treated prior to stress with the NOP agonist Ro 65-6570, and immobility time in the forced swimming task and corticosterone levels were measured. Additionally, the role of endogenous glucocorticoids and CRF was investigated using the glucocorticoid receptor antagonist mifepristone and the CRF1 antagonist antalarmin in the mediation of the effects of Ro 65-6570. RESULTS: The NOP agonist in a dose-dependent manner further increased the immobility of mice in the second swimming session compared to vehicle. By contrast, under the same conditions, the administration of the NOP antagonist SB-612111 before stress reduced immobility, while the antidepressant nortriptyline was inactive. Concerning in-serum corticosterone in mice treated with vehicle, nortriptyline, or SB-612111, a significant decrease was observed after re-exposition to stress, but no differences were detected in Ro 65-6570-treated mice. Administration of mifepristone or antalarmin blocked the Ro 65-6570-induced increase in the immobility time in the second swimming session. CONCLUSIONS: Present findings suggest that NOP agonists increase vulnerability to depression by hyperactivating the HPA axis and then increasing stress circulating hormones and CRF1 receptor signaling.
Assuntos
Cicloeptanos , Imidazóis , Peptídeos Opioides , Piperidinas , Receptores Opioides , Compostos de Espiro , Camundongos , Animais , Receptores Opioides/fisiologia , Peptídeos Opioides/metabolismo , Glucocorticoides/farmacologia , Nortriptilina/farmacologia , Receptor de Nociceptina , Corticosterona/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Mifepristona/farmacologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Stress induces diverse effects on sexual behavior, ranging from enhanced execution to the complete abolishment of sexual interaction. However, it is not clear whether some characteristics intrinsic to the individual that experiences stress could also explain this differential effect. This study seeks to relate sexual execution to susceptibility to stress (as post-stress sexual motivation). To this end, we designed a three-session experimental paradigm. In the first session, male rats were allowed to copulate with a female. In the second, the male rats received electric foot shocks as they attempted to approach the female. The third and final session was used to determine the effects of stress on sexual behavior by separating the rats into two groups: a motivation-impaired group (rats that did not cross to achieve copulation), and an unimpaired group (rats that did cross). Mount latency was affected immediately by stress in both groups, though only the non-crossing group presented a reduced number of copulatory events. The rats that did not cross showed slower-paced sexual execution even before stress was applied compared to the rats that crossed. These results show that rats that are more susceptible to stress present higher ejaculation latency even before the application of stress.