Des-acyl ghrelin reduces alcohol intake and alcohol-induced reward in rodents.
Transl Psychiatry
; 14(1): 277, 2024 Jul 04.
Article
em En
| MEDLINE
| ID: mdl-38965230
ABSTRACT
The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recompensa
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Consumo de Bebidas Alcoólicas
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Dopamina
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Área Tegmentar Ventral
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Grelina
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Núcleo Accumbens
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suécia