Simultaneous Changes in Sleep, qEEG, Physiology, Behaviour and Neurochemistry in Rats Exposed to Repeated Social Defeat Stress

Abstract

Depression is a heterogeneous disorder characterized by alterations at psychological, behavioural, physiological, neurophysiological, and neurochemical levels. Social stress is a prevalent stress in man, and the repeated social defeat stress model in rats has been proposed as being the rodent equivalent to loss of control, which in subordinate animals produces alterations that resemble several of the cardinal symptoms found in depressed patients. Here, rats followed a resident-intruder protocol for 4 consecutive days during which behavioural, physiological, and electroencephalographic (EEG) parameters were simultaneously monitored in subordinate rats. On day 5, prefrontal dopamine (DA) and hippocampal serotonin (5-HT) as well as corticosterone were measured in submissive rats that had visual, acoustic, and olfactory (but no physical) contact with a dominant, resident conspecific rat. Socially defeated rats demonstrated increases in ultrasonic vocalizations (20-25 KHz), freezing, submissive defensive behaviour, inactivity, and haemodynamic response, while decreases were found in repetitive grooming behaviour and body weight. Additionally, alterations in the sleep-wake architecture were associated with reduced active waking, enhanced light sleep, and increased frequency of transitions from light sleep to quiet wakefulness, indicating sleep instability. Moreover, the attenuation of EEG power over the frequency range of 4.2-30 Hz, associated with a sharp transient increase in delta oscillations, appeared to reflect increased brain activity and metabolism in subordinate animals. These EEG changes were synchronous with a marked increase in body temperature and a decrease in locomotor activity. Furthermore, psychosocial stress consistently increased 5-HT, DA, and corticosterone levels.The increased levels of cortical DA and hippocampal 5-HT during social threat may reflect a coping mechanism to promote alertness and psychological adaptation to provocative and threatening stimuli. These neurophysiological changes are hypothesized to be the consequence of dynamics in monoamine systems, which could be useful markers for disease progression in the aetiology of depression.

Time-of-day-dependent adaptation of the HPA axis to predictable social defeat stress

“…In an earlier paper we reported that SDL results in altered diurnal activity patterns and increased body temperature in the early morning (Bartlang et al 2015). In line with this, it was recently shown in rats that mild chronic subordination leads to reduced activity, altered sleeping patterns and increased body temperature, which suggests an increased metabolic rate as response to SDL (Ahnaou & Drinkenburg 2016), which is also reported in squirrels (Johren et al 1991, Kramer et al 1999. In line with Gorka and Adamik (1993), SDD did not influence bodyweight, but was accompanied by a reduction in food intake, pointing to an anabolic effect of stress during the active phase that is compensated by a reduction in energy intake.…”

Serotonin Signaling Trough Prelimbic 5-HT1A Receptors Modulates CSDS-Induced Behavioral Changes in Adult Female Voles

“…More recently, 4 days of social defeat stress were consistently shown to increase 5-HT levels in the hippocampus (Ahnaou and Drinkenburg, 2016). The inconsistency of 5-HT levels observed following social defeat stress may be due to observed different duration of social defeat stress.…”

A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances

“…In humans, psychosocial stressors are among the major sources of stress. In rodents, social stress—in particular, a conflict with an aggressive mouse—has been shown to disrupt sleep ( 18 – 26 ). These alterations in the sleep architecture caused by social stress may result from interactions between stress and sleep regulatory circuits.…”