PMID:30217553

Citation	'Cruz-Martínez, AM, Tejas-Juárez, JG, Mancilla-Díaz, JM, Florán-Garduño, B, López-Alonso, VE and Escartín-Pérez, RE (2018) CB1 receptors in the paraventricular nucleus of the hypothalamus modulate the release of 5-HT and GABA to stimulate food intake in rats. Eur Neuropsychopharmacol '
Abstract	Endocannabinoids and their receptors not only contribute to the control of natural processes of appetite regulation and energy balance but also have an important role in the pathogenesis of obesity. CB1 receptors (CB1R) are expressed in several hypothalamic nuclei, including the paraventricular nucleus (PVN), where induce potent orexigenic responses. Activation of CB1R in the PVN induces hyperphagia by modulating directly or indirectly orexigenic and anorexigenic signals; however, interaction among these mediators has not been clearly defined. CB1R mRNA is expressed in serotonergic neurons that innervate the PVN, and activation of 5-HT receptors in the PVN constitutes an important satiety signal. Some GABAergic terminals are negatively influenced by 5-HT, suggesting that the hyperphagic effect of CB1R activation could involve changes in serotonergic and GABAergic signaling in the PVN. Accordingly, the present study was aimed to characterize the neurochemical mechanisms related to the hyperphagic effects induced by activation of CB1R in the PVN, studying in vitro and in vivo changes induced by direct activation these receptors. Here, we have found that the neurochemical mechanisms activated by stimulation of CB1 receptors in the PVN involve inhibition of 5-HT release, resulting in a decrease of serotonergic activity mediated by 5-HT and 5-HT receptors and inducing disinhibition of GABA release to stimulate food intake. In conclusion, these neurochemical changes in the PVN are determinant to the cannabinoid-induced stimulation of food intake. Our findings provide evidence of a functional connection among CB1R and serotonergic and GABAergic systems on the control of appetite regulation mediated by endocannabinoids.
Links	PubMed Online version:10.1016/j.euroneuro.2018.08.002
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:CNR1		GO:0014054: positive regulation of gamma-aminobutyric acid secretion	ECO:0000314:		P		Figure 2 shows that when a CB1 agonist was infused in rats , GABA secretion increased whereas when a CB1 antagonist was introduced GABA secretion was not modified.	complete CACAO 13360
RAT:CNR1		GO:0014063: negative regulation of serotonin secretion	ECO:0000315:		P		Figure 3 shows that when a CB1 agonist is infused, 5-HT secretion decreased wheres when a CB1 antagonist is infused 5-HT secretion was unmodified compared to controls. Cannabinoid receptor 1, and CB1 Rattus norvegicus (Rat).	complete CACAO 13361
RAT:5HT1A		GO:0014053: negative regulation of gamma-aminobutyric acid secretion	ECO:0000315:		P		Figure 5 shows that when 5-HT 1a(8-OH-DPAT) is activated the up regulation of GABA secretion due to CB1 activation is blocked. 5-hydroxytryptamine receptor 1A, and 5-HT1A, Rattus norvegicus (Rat)	complete CACAO 13365
RAT:5HT1B		GO:0014053: regulation of gamma-aminobutyric acid secretion	ECO:0000314:		P		Figure 6 shows that when 5-HT 1b (CP 93129) is activated the up regulation of GABA secretion due to CB1 activation is blocked. Rat	complete CACAO 13366

References

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