What question did this study set out to answer?

This research aims to understand how hyperactivity in the nucleus accumbens and dysfunction in the mPFC–NAc circuit contribute to self-injurious behavior in rats.

July 17, 2026International Journal of Molecular Sciences0 citationsOpen Access

Nucleus Accumbens Hyperactivity and mPFC–NAc Circuit Dysfunction Promote Self-Injurious Behavior in Rats

YCYanmei ChenKunming University of Science and Technology ZZZhonghui ZuoKunming University of Science and Technology DLDi LuoKunming University of Science and Technology

Key Points

This research aims to understand how hyperactivity in the nucleus accumbens and dysfunction in the mPFC–NAc circuit contribute to self-injurious behavior in rats.
Used an inducible self-injurious behavior rat model to study synaptic modifications.
Administered muscimol into the endopeduncular nucleus and measured changes in AMPAR expression and phosphorylation levels.
Investigated effects of modulating NAc activity using various receptor agonists or antagonists and inhibiting the mPFC–NAc pathway.
Total GluA1 expression and phosphorylated GluA1 were decreased in mPFC, VTA, and NAc at 1 hour post-inhibition.
Hyperactivation of the NAc increased self-injurious behavior when EP was inhibited by 0.2 μg/side muscimol.
Inhibiting the mPFC–NAc pathway resulted in larger wound areas in rats exhibiting self-injurious behavior.

Abstract

Self-injurious behavior (SIB) is a devastating and potentially life-threatening action with high prevalence in adolescents and patients with neuropsychiatric disorders. Accumulating evidence indicates that disruptions in multiple cellular and circuit mechanisms underlie vulnerability to SIB. We used an inducible SIB rat model to study synaptic modification during SIB. At 0.5 and 1 h after bilateral injection of muscimol (1.0 μg/side) into the rat endopeduncular nucleus (EP, a rodent homolog of the internal globus pallidus (GPi)), which induced SIB in rats, expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) and the phosphorylation of GluA1 at Ser831 and Ser845 were tested in the lateral habenula (LHb), ventral tegmental area (VTA), nucleus accumbens (NAc), amygdala, and medial prefrontal cortex (mPFC) of the rat brain. We also tested if modulation of NAc activity with a GABAA receptor agonist or antagonist or dopamine receptor agonist or antagonist or inhibiting the mPFC–NAc pathway affected SIB in rats. At 1 h after EP inhibition, total GluA1 expression and phosphorylated GluA1 were decreased in the mPFC, VTA, and NAc, but were increased in the amygdala compared with control rats. When the EP was inhibited by 0.2 μg/side muscimol, hyperactivation of the NAc increased SIB in rats. However, if the EP was inhibited by 1.0 μg/side muscimol, hyperactivation of the NAc had no effects on SIB. Inhibiting the mPFC–NAc pathway increased wound areas in rats with SIB. At the onset of SIB, excitatory synaptic transmission is simultaneously dampened in the reward and control circuitry (VTA, NAc, mPFC) and potentiated in the aversion circuitry (amygdala), indicating that SIB is associated with molecular signatures suggestive of a shift from reward to threat processing. Hyperactivation of the NAc increased SIB incidence in rats, but administration of dopamine receptor agonists and antagonists into the NAc did not significantly affect the incidence of SIB in this study. These findings provide a novel mechanistic perspective on SIB, offering a basis for the treatment of SIB.

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