Activation of PAR1 in the lateral hypothalamus of rats enhances food intake and REMS through CB1R.
The activation of protease-activated receptor 1 (PAR1) in cultured rat hippocampal neurons triggers synaptic retrograde signaling through the endocannabinoid 2-arachidonoylglycerol, thereby activating the cannabinoid receptor 1 (CB1R). CB1R is a metabotropic receptor activated by marihuana and endocannabinoids that suppresses neurotransmitter release. Also, activation of the CB1R increases rapid eye movement sleep (REMS) and food intake. The lateral hypothalamus is a crucial structure to modulate both feeding and waking. To evaluate the effect of PAR1 stimulation in the lateral hypothalamus on food intake and on the sleep-waking cycle, we implanted rats with electrodes, for recording sleep, and cannulae, to administer S1820, a selective PAR1 agonist peptide, bilaterally into the lateral hypothalamus. To determine whether the effects induced by PAR1 stimulation were mediated by CB1R activation, we administered AM251, a CB1R inverse agonist, to block S1820 effects. Our results show that the stimulation of PAR1 into the lateral hypothalamus increases both food intake and REMS and such effects were prevented by AM251, indicating that PAR1 modulates both food intake and the sleep-waking cycle, in the lateral hypothalamus, through CB1R activation. This study shows novel behavioral changes induced by PAR1 activation and further supports the notion that endocannabinoids are food intake and REMS promoters.
Laboratory of Cannabinoids, Department of Physiology, School of Medicine, National Autonomus University of México-UNAM, DF, México.
Marcel
M
Pérez-Morales
Ilia
I
Alvarado-Capuleño
Ana M
AM
López-Colomé
Mónica
M
Méndez-Díaz
Alejandra E
AE
Ruiz-Contreras
Oscar
O
Prospéro-García
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D004435:Eating / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D012895:Sleep, REM / Q000502:physiology*
D043884:Receptor, Cannabinoid, CB1; D044463:Receptor, PAR-1