RESUMEN
The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear protein that plays an essential role in diverse neurobiological processes. However, the role of PPARα on the sleep modulation is unknown. Here, rats treated with an intrahypothalamic injection of Wy14643 (10µg/1µL; PPARα agonist) enhanced wakefulness and decreased slow wave sleep and rapid eye movement sleep whereas MK-886 (10µg/1µL; PPARα antagonist) promoted opposite effects. Moreover, Wy14643 increased dopamine, norepinephrine, serotonin, and adenosine contents collected from nucleus accumbens. The levels of these neurochemicals were diminished after MK-886 treatment. The current findings suggest that PPARα may participate in the sleep and neurochemical modulation.
Asunto(s)
Monoaminas Biogénicas/metabolismo , Núcleo Accumbens/metabolismo , PPAR alfa/metabolismo , Sueño/fisiología , Adenosina/metabolismo , Animales , Dopamina/metabolismo , Indoles/farmacología , Masculino , Norepinefrina/metabolismo , Núcleo Accumbens/efectos de los fármacos , PPAR alfa/agonistas , PPAR alfa/antagonistas & inhibidores , Pirimidinas/farmacología , Ratas Wistar , Serotonina/metabolismo , Sueño/efectos de los fármacos , Fases del Sueño/efectos de los fármacos , Fases del Sueño/fisiologíaRESUMEN
Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10µg/1µL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD.
Asunto(s)
Adenosina/metabolismo , Cannabidiol/farmacología , Espacio Extracelular/metabolismo , Hipotálamo/efectos de los fármacos , Núcleo Accumbens/metabolismo , Animales , Espacio Extracelular/efectos de los fármacos , Masculino , Microinyecciones , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The endocannabinoid system comprises amides, esters and ethers of long chain polyunsaturated fatty acids. Narachidonoylethanolamide (anandamide; ANA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids (endocannabinoids) ligands for the cannabinoid family of G-protein-coupled receptors named CB1 and CB2. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and behave as retrograde signaling messengers, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters systems. The two principal enzymes that are responsible for the metabolism of ANA and 2-AG are fatty acid amide hydrolase and monoacylglycerol lipase, respectively. Pharmacological experiments have shown that the administration of endocannabinoids induce cannabimimetic effects, including sleep promotion. This review will focus on some of the current evidence of the pharmacological potential of the endocannabinoid system on sleep modulation.