PET neuroimaging reveals upregulation of dopamine D2 receptor contributes to amygdaloid dysfunction in rat acute restraint stress model

Abstract

Acute stress relates to high prevalence of anxiety, depression or even sudden death. Although dopaminergic system in amygdala-medial prefrontal cortex (mPFC) circuit is hyper-responsive to stress-induced anxiety, the mechanisms that control anxiety still remains unanswered. Here, the acute restraint stress model(ARS) was established to develop anxiety-like behavior. The D2-dopamine receptor (D2R) availability in amygdala and mPFC was assessed using [¹⁸F]-fallypride positron emission tomography(PET) and immunohistochemical assay. We revealed that ARS paradigm was successfully established, as evidenced by elevated plus-maze test(EPM) and increased corticosterone release. Moreover, PET imaging displayed elevated D2R availability in the amygdala and mPFC in ARS as compared to that in the naives. PET imaging combined with immunohistochemical assay confirmed that amygdaloid D2R was significantly implicated in stress-induced anxiety. Our findings delivered valuable insights into neuromechanism of amygdaloid D2R underlying stress-induced anxiety and might have important implications for developing therapeutics for anxiety by targeting amygdaloid D2R.

Keywords: Acute restraint stress model; Amygdala; Anxiety; Medial prefrontal cortex; Positron emission tomography.