RESUMEN
Rapid eye movement sleep (REM) is increased after controllable stress (modeled by escapable footshock, ES) and decreased after uncontrollable stress (modeled by inescapable footshock, IS). Decreases in REM after IS are exacerbated by corticotropin releasing factor (CRF) and attenuated by a CRF antagonist. In this study, we trained mice with ES following injections of CRF, astressin (AST), or saline (SAL) to determine whether CRF would alter REM after ES. Male BALB/cJ mice (n=7) were implanted for recording sleep, activity and body temperature via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery, sleep following exposure to a novel chamber was recorded as a handling control (HC). The mice received one day of training with ES without injection followed by weekly training sessions in which they received counterbalanced intracerebroventricular (ICV) microinjections of either SAL or CRF (days 7 & 14) or SAL or AST (days 21 & 28) prior to ES. On each experimental day, sleep was recorded for 20 h. Compared to HC, the mice showed significantly increased REM when receiving either SAL or AST prior to ES whereas CRF prior to ES significantly reduced REM. Stress-induced hyperthermia had longer duration after ES compared to HC, and was not significantly altered by CRF or AST compared to SAL. The current results demonstrate that activity in the central CRF system is an important regulator of stress-induced alterations in REM.
Asunto(s)
Temperatura Corporal/efectos de los fármacos , Hormona Liberadora de Corticotropina/farmacología , Electrochoque/efectos adversos , Estrés Psicológico/etiología , Estrés Psicológico/fisiopatología , Análisis de Varianza , Animales , Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Hormona Liberadora de Corticotropina/uso terapéutico , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Pie/inervación , Inyecciones Intraventriculares/métodos , Ratones , Fragmentos de Péptidos/farmacología , Sueño REM/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Factores de TiempoRESUMEN
Corticotropin releasing hormone (CRH) plays a major role in central nervous system responses to stressors and has been implicated in stress-induced alterations in sleep. In the absence of stressors, CRH contributes to the regulation of spontaneous waking. We examined the effects of CRH and astressin (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse strains with differential responsiveness to stress to determine whether CRH might also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter for determining sleep via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery and habituation to handling, ICV microinjections of CRH (0.04, 0.2, and 0.4 microg), AST (0.1, 0.4, and 1.0 microg) or vehicle alone (pyrogen-free saline, 0.2 microl) were administered during the fourth hour after lights on and sleep was recorded for the subsequent 8 h. Comparisons of wakefulness and sleep were conducted across conditions and across strains. In C57BL/6J mice, REM was significantly decreased after microinjections of CRH (0.2 microg) and CRH (0.4 microg), and NREM and total sleep were decreased after microinjections of CRH (0.4 microg). CRH (0.04 microg) and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH (0.4 microg) increased wakefulness and decreased NREM, REM and total sleep. AST decreased active wakefulness and significantly increased REM at the low and high dosages. These findings demonstrate that CRH produces changes in arousal when given to otherwise undisturbed mice. Strain differences in the effects of CRH and AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to stressors and to underlying differences in the CRH system.