MPTP-İndüklenmiş Dopamin Basolateral Amigdala'da tükenme ⁇ i>via ⁇ /i> D2R Aktivasyonunun Azaltılması GABA ⁇ sub>A ⁇ /sub> Reseptörler İfadesi ve LTD İndüksiyonu Anksiyete Benzer Davranışlara Yol Açıyor.

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Anxiety disorders commonly occur in Parkinson's disease. Using field potential recording and patch-clamp recording, we evaluated influence of MPTP-reduced dopaminergic afferent in basolateral amygdala (BLA), a main region for affective regulation, on excitatory-inhibitory circuits and synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slopes at external capsule-BLA synapses were increased in MPTP-mice with decreases in paired-pulse facilitation and long-term potentiation amplitude, which were corrected by bath-application of D2R agonist quinpirole or cannabinoid type 1 receptors agonist WIN55,212-2, but not D1R agonist SKF38393. Compared to single waveform fEPSP in control mice, a multi-spike waveform fEPSP was observed in MPTP-mice with prolongation of duration and an increase in paired-pulse inhibition, which were recovered by BLA-injection of quinpirole for 2 days rather than bath-application. Density of GABA-evoked current (IGABA) in BLA principal neurons and GABAAR-α2 subunit expression were reduced in MPTP-mice, which were recovered by administration of quinpirole. Decline of PKC phosphorylation in BLA of MPTP-mice was corrected by bath-application of quinpirole, but not SKF38393. In MPTP-mice, BLA-injection of quinpirole or PKC activator PMA could recover GABAAR expression, which was sensitive to PKC inhibitor GF109203X. The impairment of long-term depression (LTD) in MPTP-mice was rescued by bath-application of GABAAR agonist muscimol or BLA-injection of quinpirole and PMA. Finally, BLA-injection of muscimol, quinpirole or PMA relieved anxiety-like behaviors in MPTP-mice. The results indicate that the MPTP-induced dopamine depletion in BLA principal neurons through reducing D2R-mediated PKC phosphorylation suppresses GABAAR expression and activity, which impairs GABAAR-mediated inhibition and LTD induction leading to anxiety-like behaviors.

İlgili konular