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Effects of Ghrelin Receptor Antagonists [D-Lys3]-GHRP-6 and YIL 781 on Impulsivity and Compulsivity in Rats Exposed to Early Maternal Deprivation
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DOI：10.1142/S2737416526500626.png)
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Abstract
En 中文
Early maternal deprivation (MD) in rats increases impulsivity and compulsivity, resembling features of behavioral addictions. We examined the effects of intranasal ghrelin receptor (GHSR-1a) antagonists [D-Lys(3)]-GHRP-6 and YIL 781 in adult male Wistar rats exposed to MD (3 h daily, postnatal days 2-12). Impulsive-like behavior was assessed using a three-arm probabilistic reinforcement task (adapted Iowa Gambling Task), and compulsivity via the marble-burying test. MD rats showed strong preference for high-magnitude/low-probability rewards and increased marble burying compared to controls. Chronic [D-Lys(3)]-GHRP-6 treatment significantly reduced risky choices (p=0.0003vs. saline), while YIL 781 further decreased risky preferences (p=0.003) and markedly lowered compulsive burying (p=0.002). Molecular docking and 500-ns molecular dynamics simulations indicated YIL 781 has higher affinity and greater complex stability with GHSR-1a (Delta G (docking) approximate to-10.3kcal/mol; Delta GGB approximate to-123.4kcal/mol) than [D-Lys(3)]-GHRP-6, with comparatively weaker binding to serotonin (5HT1a/2a/3a) and dopamine (D2/D3) receptors. These results suggest GHSR-1a blockade attenuates MD-induced maladaptive decision-making and repetitive behaviors, with YIL 781 exhibiting broader efficacy, likely due to stronger target engagement.
Keywords:
Ghrelin
compulsivity
impulsivity
[D-Lys3]-GHRP-6
YIL 781
molecular modeling
Journal
J
IF:
2.3
Papers:
98
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0
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Cited Papers