title: mGluR1/5 activation in the lateral hypothalamus increases food intake via the endocannabinoid system.
abstract: Mounting evidence has shown that glutamatergic and endocannabinoid systems in the hypothalamus regulate mammalian food intake. Stimulation of hypothalamic mGluR1/5 and CB1 receptors induces hyperphagia suggesting a possible interaction between these systems to control food intake. In addition, synthesis of endocannabinoids has been reported after mGluR1/5 stimulation in the brain. The aim of this study was to examine the potential cannabinergic activity in the food intake induction by lateral hypothalamic stimulation of mGluR1/5. Wistar albino male rats received bilateral infusions in the lateral hypothalamus (LH) of: (i) vehicle; (ii) (RS)-2-Chloro-5-hidroxyphenylglycine (CHPG; mGluR1/5 agonist); (iii) 2-AG (CB1 endogenous agonist); (iv) AM251 (CB1 antagonist); (v) tetrahydrolipstatin (THL, 1.2μg; diacyl-glycerol lipase inhibitor); and (vi) combinations of CHPG + with the other aforementioned drugs. Food intake was evaluated the first two hours after drug administration. CHPG significantly increased food intake; whereas CHPG in combination with a dose of 2-AG (with no effects on food intake) greatly increased food ingestion compared to CHPG alone. The increase induced by CHPG in food intake was prevented with AM251 or THL. These results suggest that activation of mGluR1/5 in the lateral hypothalamus induces an orexigenic effect via activation of the endocannabinoid system.
authors.affiliation: Grupo de Neurociencias, Laboratorio de Cannabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Asai
authors.initials: A
authors.lastname: Sánchez-Fuentes
authors.affiliation: Grupo de Neurociencias, Laboratorio de Cannabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.affiliation: Grupo de Neurociencias, Laboratorio de Cannabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Méndez-Díaz
authors.affiliation: Grupo de Neurociencias, Laboratorio de Cannabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Alline L
authors.initials: AL
authors.lastname: Becerril-Meléndez
authors.affiliation: Lab. Neurogenomica Cognitiva, Coord. Psicobiología y Neurociencias, Fac. Psicologia, Universidad Nacional Autónoma de México, México D.F., Mexico.
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: Ruiz-Contreras
authors.affiliation: Grupo de Neurociencias, Laboratorio de Cannabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico. Electronic address: opg@unam.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Prospéro-Garcia
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects; D063388:Endocannabinoids / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D007783:Lactones / Q000008:administration & dosage; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008297:Male; D000077403:Orlistat; D010648:Phenylacetates / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; C578937:Grm5 protein, rat; D007783:Lactones; D010648:Phenylacetates; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C103505:AM 251; D000077403:Orlistat; D008071:Lipoprotein Lipase; D005998:Glycine
keywords: 2-AG; Endocannabinoid system; Food intake-lateral hypothalamus; mGluR1/5