title: Prodepressive effect induced by microinjections of MCH into the dorsal raphe: time course, dose dependence, effects on anxiety-related behaviors, and reversion by nortriptyline.
abstract: Melanin-concentrating hormone (MCH) administered within the rat dorsal raphe nucleus (DRN) has been shown to elicit prodepressive behaviors in the forced-swim test. The present study was designed to evaluate the time course (30 and 60 min) and dose dependence (25-100 ng) of this effect, and whether it would be antagonized by an intra-DRN microinjection of the MCH-1 receptor antagonist ATC0175 (ATC, 1 mmol/l) or intraperitoneal pretreatment with the noradrenergic antidepressant nortriptyline (20 mg/kg). The results showed that the behavioral effect of MCH was time and dose dependent as immobility was increased, and climbing decreased, only by the 50 ng MCH dose at T30. The effect was mediated by MCH-1 receptors as a significant blockade of this behavioral response was observed in ATC-pretreated animals. ATC did not by itself modify animal behavior. Nortriptyline also prevented the prodepressive-like effect of MCH. Concomitantly, the effect of MCH (50 ng) at T30 on anxiety-related behaviors was assessed using the elevated plus-maze. Interestingly, these behaviors were unchanged. In conclusion, MCH administration within the DRN elicits, through the MCH-1 receptor, a depression-related behavior that is not accompanied by changes in anxiety and that is prevented by a noradrenergic antidepressant.
authors.affiliation: aLaboratory of Cell Biology bDepartment of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable cDepartment of Physiology, Facultad de Medicina, Montevideo, Uruguay.
authors.forename: Jessika
authors.initials: J
authors.lastname: Urbanavicius
authors.forename: Patricia
authors.initials: P
authors.lastname: Lagos
authors.forename: Pablo
authors.initials: P
authors.lastname: Torterolo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003514:Cyclohexylamines / Q000494:pharmacology; D003863:Depression / Q000139:chemically induced* / Q000503:physiopathology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007028:Hypothalamic Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008543:Melanins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D009661:Nortriptyline / Q000494:pharmacology; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D002492:Central Nervous System Depressants; D003514:Cyclohexylamines; D007028:Hypothalamic Hormones; C491208:MCHR1 protein, rat; D008543:Melanins; C501654:N-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3,4-difluorobenzamide; D010907:Pituitary Hormones; D011799:Quinazolines; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone; D009661:Nortriptyline