RESUMEN
Chronic reduction of sleep time in children and adolescents has been related to increased incidence of anxiety and depression. In rats, protocols of protracted sleep deprivation or chronic sleep restriction (CSR) are considered a stressor. In previous studies we showed that post-weaning CSR in male rats induces anxiety-like behaviour and changes in neurotransmission in emotion-related brain areas. In the present study we examined whether the effects of this adversity are sex-dependent. Twenty-two litters, containing four males and four females were distributed into control (CTL) and CSR groups. CSR began on postnatal day (PND) 21 and lasted for 21 days; each day the animals were placed onto small platforms immersed in water for 18 h and were allowed to sleep freely in their home-cages for the remaining 6 h. Throughout the CSR, all animals underwent the sucrose splash test once/week to assess their self-care and hedonic behaviours. Body weight was measured on PNDs 21 and 42. At the end of CSR period, the adolescents were allowed to sleep freely for 2 days, after which, behavioural tests began. Within each litter, one male and one female (pair) were not tested and provided blood and brain for determination of basal corticosterone (CORT) levels and hippocampal BDNF. One pair was tested in the sucrose preference test (SPT), one pair on the elevated plus maze (EPM) and one pair in the forced swim test (FST). CORT was measured after all conditions. CSR impaired self-care behaviour and body weight gain in males and females and increased relative adrenal weight only in males. There were no changes in sucrose intake in the SPT; CSR females displayed less immobility in the FST and CSR males displayed more anxiety-like behaviour in the EPM. CORT levels were similar between CTL and CSR males, whilst lower in CSR females than CTL ones in all experimental conditions. No changes in BDNF levels were detected in the dorsal hippocampus of CSR rats. The results indicate that CSR impaired self-care behaviour in both sexes, but only males displayed anxiety-like behaviour, whilst sleep recovery in females appeared to normalise their behaviour.
RESUMEN
Loneliness affects group-living mammals triggering a cascade of stress-dependent physiological disorders. Indeed, social isolation stress is a major risk factor for several neuropsychiatric disorders including anxiety and depression. Furthermore, social isolation has a negative impact on health and fitness. However, the neurobiological consequences of long-term chronic social isolation stress (LTCSIS) manifested during the adulthood of affected individuals are not fully understood. Our study assessed the impact of LTCSIS and social buffering (re-socialization) on the behavioural performance and social-affective brain-related proteins in diurnal, social, and long-lived Octodon degus (degus). Thereby, anxiety-like and social behaviour, and social recognition memory were assessed in male and female animals subjected to a variety of stress-inducing treatments applied from post-natal and post-weaning until their adulthood. Additionally, we evaluated the relationship among LTCSIS, Oxytocin levels (OXT), and OXT-Ca2+-signalling proteins in the hypothalamus, the hippocampus, and the prefrontal cortex. Our findings suggest that LTCSIS induces anxiety like-behaviour and impairs social novelty preference whereas sociability is unaffected. On the other hand, re-socialization can revert both isolation-induced anxiety and social memory impairment. However, OXT and its signalling remained reduced in the abovementioned brain areas, suggesting that the observed changes in OXT-Ca2+ pathway proteins were permanent in male and female degus. Based on these findings, we conclude degus experience social stress differently, suggesting the existence of sex-related mechanisms to cope with specific adaptive challenges.
RESUMEN
Histamine H3 receptors (H3R) have attracted interest of research groups as drug target to several CNS disorders. Data suggests that H3R antagonists exert neuroprotective, cognitive enhancement and antidepressant effects in rodents. The LINS01 compounds were reported as selective H3R antagonists, but their effects on memory, anxiety-like behaviour and spontaneous locomotor activity were not evaluated to date. Therefore, this study employed the plus-maze discriminative avoidance task (PM-DAT) to assess concomitantly the effects of LINS01 compounds on short- and long-term memory, anxiety-like behaviour and spontaneous locomotor activity. Thirty-eight adult male Wistar rats were divided into five groups (nâ¯=â¯7-8 per group) according to the treatment. The animals were treated with donepezil (1â¯mg/kg) and clobenpropit (3â¯mg/kg) (reference compounds), and with two LINS01 compounds at doses of 5â¯mg/kg (LINS01003 and LINS01004), and then submitted to the PM-DAT protocol. Saline (vehicle) was used as control group. The behavioural data showed that anxiety-like behaviour, spontaneous locomotor activity and memory effects (short- and long-term) were not affected by the treatment with LINS01004 or clobenpropit. Conversely, treatment with LINS01003 and donepezil impaired the maintenance of discriminative avoidance long-term memory, a hippocampal-dependent memory. Donepezil-treated rats also showed decreased spontaneous locomotor activity and anxiolytic-like effects. In summary, considering that hippocampal damage and memory impairment are associated with Alzheimer's disease (AD), this work brought important findings regarding the contribution of the histamine system to the effects of LINS01 compounds on memory, anxiety and motility, and suggests that H3R antagonism had no effects on anxiety-like behaviour and do not impair discriminative avoidance memory. Furthermore, the findings herein raise new questions about donepezil's function in an "impaired" system such as AD, since it prevented the long-term memory formation in healthy rats.