GALR1/GALR2 Knockdown rats block the Depression and Anxiogenic effects induced by GAL(1-15): The Heterodimer GALR1/GALR2 as a target of GAL(1-15)

The Galanin N-terminal fragment(1-15) [GAL(1-15)] induces depressant-and anxiogenic-like actions. In this work, we have studied the role of GALR2 and GALR1 on the effects of GAL(1-15) in the Forced Swimming Test (FST) and Open Field Test (OFT) using siRNA GALR2 and GALR1 knockdown rats. Rats were in...

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Veröffentlicht in:Neuropeptides (Edinburgh) 2017-10, Vol.65, p.151-151
Hauptverfasser: Millón, Carmelo, Antonio, Flores-Burgess, Manuel, Narvaez, Borroto-Escuela Dasiel, O, Luis, Santín, Concención, Parrado, Angel, Narvaez Jose, Kjell, Fuxe, Zaida, Diaz-Cabiale
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container_issue
container_start_page 151
container_title Neuropeptides (Edinburgh)
container_volume 65
creator Millón, Carmelo
Antonio, Flores-Burgess
Manuel, Narvaez
Borroto-Escuela Dasiel, O
Luis, Santín
Concención, Parrado
Angel, Narvaez Jose
Kjell, Fuxe
Zaida, Diaz-Cabiale
description The Galanin N-terminal fragment(1-15) [GAL(1-15)] induces depressant-and anxiogenic-like actions. In this work, we have studied the role of GALR2 and GALR1 on the effects of GAL(1-15) in the Forced Swimming Test (FST) and Open Field Test (OFT) using siRNA GALR2 and GALR1 knockdown rats. Rats were injected with GAL(l-15)3nmol, GALR2antagonist M871 3nmol in combination or alone 15 before the test. The time of immobility.climbing and swimming were recorded in FST and Time and entries in the center in the OFT. In other experiment, rats were injected Intracerebroventricular (icv) with siRNA-GALR2 or siRNA-GALRl to generate the GALRknockdown rats. These knockdown rats were used in the OFT/FST after receiving icv GAL(l-15)3nmol 15min before the test Vehicle was used as control. In the FST, M871 significantly blocked the increased immobility (p
doi_str_mv 10.1016/j.npep.2017.02.074
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In this work, we have studied the role of GALR2 and GALR1 on the effects of GAL(1-15) in the Forced Swimming Test (FST) and Open Field Test (OFT) using siRNA GALR2 and GALR1 knockdown rats. Rats were injected with GAL(l-15)3nmol, GALR2antagonist M871 3nmol in combination or alone 15 before the test. The time of immobility.climbing and swimming were recorded in FST and Time and entries in the center in the OFT. In other experiment, rats were injected Intracerebroventricular (icv) with siRNA-GALR2 or siRNA-GALRl to generate the GALRknockdown rats. These knockdown rats were used in the OFT/FST after receiving icv GAL(l-15)3nmol 15min before the test Vehicle was used as control. In the FST, M871 significantly blocked the increased immobility (p&lt;0.001) and decreased climbing (p&lt;0.01) induced by GAL(1-15). In the OFT M871 also significantly decreased the number of entries (p&lt;0.001) and time spent in the center (p&lt;0.05) mediated by GAL(1-15). Down-regulation of GALR2 or GALR1 by siRNA was sufficient to block the effect of GAL(1-15) in behavioural tests. Thus, CAL(1-15)3nmol lacked effect on the immobility.climbing and swimming time in the FST. The same effect was observed in the number of entries and time spent in the center in the OFT. These results indicated that GALR1 and GALR2 are involved in the GAL(1-15) depression-and anxiogenic-like effects suggesting that GAL(1-15) could act through GALR1/GALR2 heteroreceptor complex. 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In this work, we have studied the role of GALR2 and GALR1 on the effects of GAL(1-15) in the Forced Swimming Test (FST) and Open Field Test (OFT) using siRNA GALR2 and GALR1 knockdown rats. Rats were injected with GAL(l-15)3nmol, GALR2antagonist M871 3nmol in combination or alone 15 before the test. The time of immobility.climbing and swimming were recorded in FST and Time and entries in the center in the OFT. In other experiment, rats were injected Intracerebroventricular (icv) with siRNA-GALR2 or siRNA-GALRl to generate the GALRknockdown rats. These knockdown rats were used in the OFT/FST after receiving icv GAL(l-15)3nmol 15min before the test Vehicle was used as control. In the FST, M871 significantly blocked the increased immobility (p&lt;0.001) and decreased climbing (p&lt;0.01) induced by GAL(1-15). In the OFT M871 also significantly decreased the number of entries (p&lt;0.001) and time spent in the center (p&lt;0.05) mediated by GAL(1-15). Down-regulation of GALR2 or GALR1 by siRNA was sufficient to block the effect of GAL(1-15) in behavioural tests. Thus, CAL(1-15)3nmol lacked effect on the immobility.climbing and swimming time in the FST. The same effect was observed in the number of entries and time spent in the center in the OFT. These results indicated that GALR1 and GALR2 are involved in the GAL(1-15) depression-and anxiogenic-like effects suggesting that GAL(1-15) could act through GALR1/GALR2 heteroreceptor complex. These findings may give the basis for the development of novel therapeutic drugs targeting GAL(1-15) system for treatment of depression and anxiety disorders.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><doi>10.1016/j.npep.2017.02.074</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Anxiety
Climbing
Drug delivery
Drug development
Galanin
Laboratory animals
Mental depression
Neuropeptides
Open-field behavior
Psychotropic drugs
siRNA
Swimming
title GALR1/GALR2 Knockdown rats block the Depression and Anxiogenic effects induced by GAL(1-15): The Heterodimer GALR1/GALR2 as a target of GAL(1-15)
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