2-Arachidonoylglycerol into the lateral hypothalamus improves reduced sleep in adult rats subjected to maternal separation

Abstract

We have previously reported that maternal separation (MS) for 3 h daily during the first two postnatal weeks increases wakefulness, whereas it reduces sleep in rats. Oleamide, an agonist of the cannabinoid receptor type 1, increases sleep in MS rats to such a level that we cannot differentiate their sleep patterns from those of their non-MS (NMS) siblings. However, 2-arachidonoylglycerol (2-AG), an endocannabinoid, infused into the lateral hypothalamus of NMS rats at the beginning of the dark phase of the cycle increases rapid eye movement sleep and the expression of c-Fos on the rapid eye movement sleep promoting melanin-concentrating hormone neurons. We recorded the sleep-wake cycle of adult rats subjected to MS for 3 h daily from postnatal days 2 to 16, as well as in their NMS siblings. Besides the electrodes for recording the sleep-wake cycle, a couple of cannulae aimed bilaterally to the lateral hypothalamus were implanted to infuse 2-AG. We found that administration of 2-AG into the lateral hypothalamus of MS rats at the beginning of the light phase of the cycle restores sleep, whereas sleep and wakefulness of NMS rats under 2-AG infusion do not show any significant change.

Low brain endocannabinoids associated with persistent non-goal directed nighttime hyperactivity after traumatic brain injury in mice

“…It is of note that the endocannabinoid system underlies a photoperiodic diurnal regulation 67 . AEA, OEA and PEA at highest in the dark phase whereas 1,2-AG raises in the light phase 68,69 and is supposed to induce sleep 70 . The deficit of AEA, OEA and PEA may therefore manifest mainly in hyperactivity during the dark phase.…”

Stress & sleep: A relationship lasting a lifetime

“…Several methods to induce early-life stress have been used in animal models, either before (prenatal stress) or immediately after (postnatal stress) birth. Applied prenatal stressors include maternal restraining (Dugovic et al, 1999;Rao et al, 1999), malnutrition (Datta et al, 2000;Duran et al, 2006), exposure to various stimuli (bright light (Koehl et al, 1999), or hypoxia (Joseph et al, 2002), whereas cross-fostering (Santangeli et al, 2016) and, particularly, maternal separation (Feng et al, 2007;Perez-Morales et al, 2014;Sampath et al, 2014;Tiba et al, 2003;Tiba et al, 2004Tiba et al, , 2008 have been used as protocols for postnatal stress.…”

Cannabinoids, Endocannabinoids and Sleep

“…Direct injection of 2-AG into the lateral hypothalamus, a brain region that contains both awake-promoting orexin neurons and sleep-promoting melanin-concentrating hormone (MCH) neurons (Yamashita and Yamanaka, 2017 ), has been shown to increase REM sleep, likely by increasing activity in MCH-producing neurons (Perez-Morales et al, 2013 ). This treatment also mitigates sleep disruption due to early-life stress in rats (Perez-Morales et al, 2014 ). The hippocampus is also known to be involved in sleep and its role in memory consolidation (Marshall and Born, 2007 ).…”