A new "sudden fright paradigm" to explore the role of (epi)genetic modulations of the DAT gene in fear-induced avoidance behavior.
Genes Brain Behav
; 20(4): e12709, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33070435
ABSTRACT
Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT-KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive-like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX-HET), compared to HET rats born from WT-mother and KO-father (MAT-HET), implementing the role of maternal care on DAT modulation. We developed a "sudden fright" paradigm (based on dark-light test) to study reaction to fearful inputs in the DAT-KO, MAT-HET, MIX-HET, and WT groups. Rats could freely explore the whole 3-chambers apparatus; then, they were gently confined in one room where they experienced the fright; finally, they could freely move again. As expected, after the fearful stimulus only MAT-HET rats showed a different behavior consisting of avoidance towards the fear-associated chamber, compared to WT rats. Furthermore, ex-vivo immuno-fluorescence reveals higher prefrontal DAT levels in MAT-HET compared to MIX-HET and WT rats. Immuno-fluorescence shows also a different histone deacetylase (HDAC) enzymes concentration. Since HDAC concentration could modulate gene expression, within MAT-HET fore brain, the enhanced expression of DAT could well impair the corticostriatal-thalamic circuit, thus causing aberrant avoidance behavior (observed only in MAT-HET rats). DAT expression seems to be linked to a simply different breeding condition, which points to a reduced care by HET dams for epigenetic regulation. This could imply significant prefronto-cortical influences onto the emotional processes hence an excessively frightful response, even to mild stressful agents, may draw developmental trajectories toward anxious and depressed-like behavior.
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Base de dados:
MEDLINE
Assunto principal:
Transtorno do Deficit de Atenção com Hiperatividade
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Aprendizagem da Esquiva
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Comportamento Animal
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Proteínas da Membrana Plasmática de Transporte de Dopamina
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Medo
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article