Clinical and preclinical studies suggest that early-life stress can increase the risk of developing ethanol use disorder later in life. Although the endocannabinoid (eCB) system plays a role in stress-related behaviors and ethanol consumption, it remains unclear whether the eCB system is affected in response to a combination of both factors. By using male and female adolescent C57BL/6J mice subjected to a maternal separation (MS) stress paradigm from postnatal day (PND) 1 to 14, we explored (1) the consequences of early-life stress experiences on ethanol consumption in adolescent mice and (2) how these events affect the eCB system and neuronal activation in brain regions associated with the reward system. In Experiment 1, we found that MS increased involuntary ethanol consumption specifically during the first exposure to the drug (during a 24 h-long trial on PND 28) and decreased the active/inactive nose poke ratio (discrimination index) specifically when mice were subjected to 1 h-sessions (PND 82-86) in an operant ethanol self-administration paradigm. In Experiment 2, during a two-bottle free choice paradigm, we found that MS increased mice preference for high ethanol concentrations (15 % and 20 %) but not lower ethanol concentrations (5 % and 10 %). Except for Mgll gene expression in the dorsal striatum (DS) in Experiment 2, no statistically significant effects of MS were observed regarding neuronal activation on the prefrontal cortex, DS, globus pallidus, and substantia nigra following a binge operant ethanol self-administration session (Experiment 1) or the eCB system molecules (Cnr1 and Faah gene expression) in the DS (Experiment 2).
Chronic insomnia (CI) is a common sleep disorder in middle-aged and elderly individuals. Long-term sleep deprivation can lead to physical, mental, and cognitive damage. Resting-state networks (RSNs) in the brain are closely linked to cognition and behavior. Therefore, we investigated changes in RSNs to explore behavioral and cognitive abnormalities in middle-aged and elderly CI patients. Resting state functional magnetic resonance imaging (rs-fMRI) and independent component analysis were used to study the intrinsic functional connectivity (FC) of the RSNs in 36 CI patients (20 CI with cognitive impairment (CI-I) patients and 16 CI without cognitive impairment (CI-N) patients) and 20 healthy controls (HC). Two-sample t-tests were used to compare RSNs differences between CI and HC groups and the RSNs differences between CI-I and CI-N groups. Partial correlation analysis was used to explore the relationship between the significant abnormal brain regions in RSN and clinical scales. Compared with HCs, CI patients showed significant differences in multiple RSNs, and FC values in two brain regions within RSNs were correlated with clinical scales. Furthermore, compared with CI-N group, CI-I group also showed significantly altered FC in multiple RSNs. Moreover, FC values in the right middle frontal gyrus within right frontal parietal network of CI-I patients were negatively correlated with the Mini-Mental State Examination scores. These results may explain hyperarousal, decreased attention and motor function impairments in CI patients. Furthermore, the aberrant alterations of RSNs in CI-I patients may play a crucial role in the onset and progression of cognitive impairment in CI patients.