Galanin N-Terminal fragment (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT in the Forced Swimming Test.
Millón-Peñuela, Carmelo,Flores-Burgess, Antonio,Narváez-Peláez, Manuel,Borroto Escuela, Dasiel Óscar,Santín-Núñez, Luis Javier,Gago-Calderón, Belén,Parrado-Romero, Concepción,Gomez de Travecedo, Isabel,Narváez-Bueno, José Ángel,Fuxe, Kjell,Díaz-Cabiale,
- Published
- 2016-07-02
- Language
- en
Abstract
Galanin and Galanin (1-15) [GAL(1-15)] are implicated in anxiety- and depression related behaviors. Moreover, Galanin modulates 5-HT1A receptor (5-HT1AR) function at autorreceptor and postsynaptic level in the brain. In this study, we have analysed the ability of GAL(1-15) to modulate the effects of the 8-OH-DPAT agonist in the Forced Swimming Test (FST). Groups of rats were assessed in the FST. In the first set of experiments, to evaluate the interactions of 8-OH-DPAT and GAL(1-15), rats received subcutaneously (s.c) the effective doses of 8-OH-DPAT (0.25mg/Kg) 60min before the test and intracerebroventricularly (icv) GAL(1-15)1nmol 15min before the tests alone or in combination. In the second set of experiments, groups of rats received s.c. 8-OH-DPAT (0.125mg/Kg), icv GAL(1-15) 1nmol and icv the GALR2 antagonist M871 3 nmol alone or in combination. The locomotor activity was analysed in the open field test. GAL(1-15) 1nmol enhanced the antidepressant-like effects mediated by the effective dose of the 8-OH-DPAT. GAL(1-15) significantly decreased the immobility (p<0.05) and climbing (p<0.05) and increased the swimming (p<0.01) behaviour induced by an effective dose of 8-OH-DPAT (0.25mg/Kg) in FST. Moreover, after coadministration of GAL(1-15) and threshold dose of 8-OH-DPAT (0.125mg/Kg) a significant decreased appeared in immobility (p<0.01) and climbing (p<0.01) and increased the swimming behavior (p<0.001) vs 8-OH-DPAT group. Moreover, M871 blocked completely this interaction. These results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT in the FST. These findings may give the basis for the development of novel therapeutic drugs. This study was supported by Junta de Andalucía CVI6476.
Full text
Galanin&N-Terminal&fragment&(1-15)&enhances&the&antidepressant&effects& of&the&5-HT1A&receptor&agonist&8-OH-DPAT&in&the&Forced&Swimming&Test.& Millón& C& 1," Flores-Burgess" A" 1," Narváez" M" 1," Borroto-Escuela" DO" 2," Santín" L" 2," Gago" B" 1," Parrado" C" 1," Gómez"de"Travecedo"I"1,"Narváez"JA"1,"Fuxe"K"2,"Díaz-Cabiale"Z"1." 1." Universidad" de" Málaga," Instituto" de" Investigación" Biomédica" de" Málaga," Facultad" de" Medicina," Departamento"de"Fisiología,"Campus"de"Teatinos"s/n,"29071"Málaga,"Spain" 2."Department of Neuroscience, Karolinska Institute, Stockholm, Sweden 3." Universidad" de" Málaga," Instituto" de" Investigación" Biomédica" de" Málaga," Facultad" de" Medicina," Departamento"de"Psicobiología,"Campus"de"Teatinos"s/n,"29071"Málaga,"Spain" " Galanin" and" Galanin" (1-15)"[GAL(1-15)]" are" implicated" in" anxiety-" and" depression" related"behaviors."Moreover,"Galanin"modulates"5-HT1A"receptor"(5-HT1AR)"function" at"autorreceptor"and"postsynaptic"level"in"the"brain."In"this"study,"we"have"analysed" the" ability" of" GAL(1-15)" to" modulate" the" effects" of" the" 8-OH-DPAT" agonist" in" the" Forced"Swimming"Test"(FST)." Groups"of"rats"were"assessed"in"the"FST."In"the"first"set"of"experiments,"to"evaluate"the" interactions" of" 8-OH-DPAT" and" GAL(1-15)," rats" received" subcutaneously" (s.c)" the" effective" doses" of" 8-OH-DPAT"(0.25mg/Kg)" 60min" before" the" test" and" intracerebroventricularly" (icv)" GAL(1-15)1nmol" 15min" before" the" tests" alone" or" in" combination."In"the"second"set"of"experiments,"groups"of"rats"received"s.c."8-OH-DPAT" (0.125mg/Kg),"icv"GAL(1-15)"1nmol"and"icv"the"GALR2"antagonist"M871"3"nmol"alone" or"in"combination."The"locomotor"activity"was"analysed"in"the"open"field"test." GAL(1-15)"1nmol"enhanced"the"antidepressant-like"effects"mediated"by"the"effective" dose"of"the"8-OH-DPAT."GAL(1-15)"significantly"decreased"the"immobility"(p<0.05)"and" climbing" (p<0.05)" and" increased" the" swimming" (p<0.01)" behaviour" induced" by" an" effective"dose"of"8-OH-DPAT"(0.25mg/Kg)"in"FST."Moreover,"after"coadministration"of" GAL(1-15)" and" threshold" dose" of" 8-OH-DPAT" (0.125mg/Kg)" a" significant" decreased" appeared" in" immobility" (p<0.01)" and" climbing" (p<0.01)" and" increased" the" swimming" behavior" (p<0.001)" vs" 8-OH-DPAT" group." Moreover," M871" blocked" completely" this" interaction." These"results"indicate"that"GAL(1-15)"enhances"the"antidepressant"effects"induced"by" 8-OH-DPAT"in"the"FST."These"findings"may"give"the"basis"for"the"development"of"novel" therapeutic"drugs." This"study"was"supported"by"Junta"de"Andalucía"CVI6476." "
