Ghrelin/GHS-R1A antagonism in memory test and its effects on central molecular signaling involved in addiction in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F23%3A43925210" target="_blank" >RIV/00216208:11120/23:43925210 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/23:10457598

Výsledek na webu

<a href="https://doi.org/10.1016/j.pbb.2023.173528" target="_blank" >https://doi.org/10.1016/j.pbb.2023.173528</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pbb.2023.173528" target="_blank" >10.1016/j.pbb.2023.173528</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ghrelin/GHS-R1A antagonism in memory test and its effects on central molecular signaling involved in addiction in rats

Popis výsledku v původním jazyce

Central ghrelin signaling seems to play important role in addiction as well as memory processing. Antagonism of the growth hormone secretagogue receptor (GHS-R1A) has been recently proposed as a promising tool for the unsatisfactory drug addiction therapy. However, molecular aspects of GHS-R1A involvement in specific brain regions remain unclear. The present study demonstrated for the first time that acute as well as subchronic (4 days) administration of the experimental GHS-R1A antagonist JMV2959 in usual intraperitoneal doses including 3 mg/kg, had no influence on memory functions tested in the Morris Water Maze in rats as well as no significant effects on the molecular markers linked with memory processing in selected brain areas in rats, specifically on the β-actin, c-Fos, two forms of the calcium/calmodulin-dependent protein kinase II (CaMKII, p-CaMKII) and the cAMP-response element binding protein (CREB, p-CREB), within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HIPP). Furthermore, following the methamphetamine intravenous self-administration in rats, the 3 mg/kg JMV2959 pretreatment significantly reduced or prevented the methamphetamine-induced significant decrease of hippocampal β-actin and c-Fos as well as it prevented the significant decrease of CREB in the NAC and mPFC. These results imply, that the GHS-R1A antagonist/JMV2959 might reduce/prevent some of the memory-linked molecular changes elicited by methamphetamine addiction within brain structures associated with memory (HIPP), reward (NAc), and motivation (mPFC), which may contribute to the previously observed significant JMV2959-induced reduction of the methamphetamine self-administration and drug-seeking behavior in the same animals. Further research is necessary to corroborate these results.

Název v anglickém jazyce

Ghrelin/GHS-R1A antagonism in memory test and its effects on central molecular signaling involved in addiction in rats

Popis výsledku anglicky

Central ghrelin signaling seems to play important role in addiction as well as memory processing. Antagonism of the growth hormone secretagogue receptor (GHS-R1A) has been recently proposed as a promising tool for the unsatisfactory drug addiction therapy. However, molecular aspects of GHS-R1A involvement in specific brain regions remain unclear. The present study demonstrated for the first time that acute as well as subchronic (4 days) administration of the experimental GHS-R1A antagonist JMV2959 in usual intraperitoneal doses including 3 mg/kg, had no influence on memory functions tested in the Morris Water Maze in rats as well as no significant effects on the molecular markers linked with memory processing in selected brain areas in rats, specifically on the β-actin, c-Fos, two forms of the calcium/calmodulin-dependent protein kinase II (CaMKII, p-CaMKII) and the cAMP-response element binding protein (CREB, p-CREB), within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HIPP). Furthermore, following the methamphetamine intravenous self-administration in rats, the 3 mg/kg JMV2959 pretreatment significantly reduced or prevented the methamphetamine-induced significant decrease of hippocampal β-actin and c-Fos as well as it prevented the significant decrease of CREB in the NAC and mPFC. These results imply, that the GHS-R1A antagonist/JMV2959 might reduce/prevent some of the memory-linked molecular changes elicited by methamphetamine addiction within brain structures associated with memory (HIPP), reward (NAc), and motivation (mPFC), which may contribute to the previously observed significant JMV2959-induced reduction of the methamphetamine self-administration and drug-seeking behavior in the same animals. Further research is necessary to corroborate these results.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA21-30795S" target="_blank" >GA21-30795S: Modulace mesolimbického ghrelinového systému - nová naděje pro léčbu závislosti na metamfetaminu?</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pharmacology, Biochemistry &amp; Behavior

ISSN

0091-3057

e-ISSN

1873-5177

Svazek periodika

224

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

173528

Kód UT WoS článku

000992445700001

EID výsledku v databázi Scopus

2-s2.0-85149484089