title: Phosphodiesterase-7 inhibition affects accumbal and hypothalamic thyrotropin-releasing hormone expression, feeding and anxiety behavior of rats.
abstract: Thyrotropin-releasing hormone (TRH) has anorexigenic and anxiolytic functions when injected intraventricularly. Nucleus accumbens (NAcc) is a possible brain region involved, since it expresses proTRH. TRH from hypothalamic paraventricular nucleus (PVN) has a food intake-regulating role. TRHergic pathways of NAcc and PVN are implicated in anxiety and feeding. Both behaviors depend on cAMP and phosphorylated-cAMP response element binding protein (pCREB) intracellular levels. Intracellular levels of cAMP are controlled by the degrading activity of phosphodiesterases (PDEs). Since TRH transcription is activated by pCREB, a specific inhibitor of PDE7B may regulate TRH-induced effects on anxiety and feeding. We evaluated the effectiveness of an intra-accumbal and intraperitoneal (i.p.) administration of a PDE7 inhibitor (BRL-50481) on rats' anxiety-like behavior and food intake; also on TRH mRNA and protein expression in NAcc and PVN to define its mediating role on the PDE7 inhibitor-induced behavioral changes. Accumbal injection of 4μg/0.3μL of PDE7 inhibitor decreased rats' anxiety. The i.p. injection of 0.2mg/kg of the inhibitor was able to increase the PVN TRH mRNA expression and to decrease feeding but did not change animals' anxiety levels; in contrast, 2mg/kg b.w inhibitor enhanced accumbal TRH mRNA, induced anxiolysis with no change in food intake. PDE7 inhibitor induced anxiolytic and anorexigenic like behavior depending on the dose used. Results supported hypothalamic TRH mediated feeding-reduction effects, and accumbal TRH mediation of inhibitor-induced anxiolysis. Thus, an i.p dose of this inhibitor might be reducing anxiety with no change in feeding, which could be useful for obese patients.
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico; School of Dietetics and Nutrition ISSSTE, Callejón Vía San Fernando 12, Col. San Pedro Apóstol, 14070 México City, Mexico.
authors.forename: M I
authors.initials: MI
authors.lastname: Valdés-Moreno
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Alcántara-Alonso
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Estrada-Camarena
authors.affiliation: Department of Neurochemistry and Neuropharmachology, Institut d'Investigacions Biòmediques de Barcelona, CSIC, IDIBAPS, CIBERNED, c/Rosselló 161, 6a, E 08036 Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Mengod
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico.
authors.forename: M I
authors.initials: MI
authors.lastname: Amaya
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Matamoros-Trejo
authors.affiliation: Department of Neuroscience Research, National Institute of Psychiatry RFM, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México City, Mexico. Electronic address: gortari@imp.edu.mx.
authors.forename: P
authors.initials: P
authors.lastname: de Gortari
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy; D000242:Cyclic AMP / Q000378:metabolism; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors*; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009574:Nitro Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D009714:Nucleus Accumbens / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D000242:Cyclic AMP; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D007453:Iodide Peroxidase; D009574:Nitro Compounds; D013449:Sulfonamides; D013973:Thyrotropin-Releasing Hormone; D000097564:Iodothyronine Deiodinase Type II; C497936:3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene
keywords: Anxiety; Feeding; Hypothalamus; N. accumbens; Phosphodiesterase; TRH