Aripiprazole and haloperidol protect neurite lesions via reducing excessive D2R-DISC1 complex formation

Prevention of Neurite Spine Loss Induced by Dopamine D2 Receptor Overactivation in Striatal Neurons

“…Confocal fluorescence resonance energy transfer (FRET) analysis was performed as described previously (Zheng et al, 2018). In the striatal neurons, anti-D2R-Alexa Fluor 488 was used as a donor dipole, while anti-DISC1-Alexa Fluor 568 was used as an acceptor dipole.…”

“…We recently reported that aripiprazole, an atypical antipsychotic drug, protects the neurite length of cortical neurons by blocking D2R signaling and uncoupling D2R-DISC1 complexes (Zheng et al, 2018). To determine whether decreasing abnormal D2R-DISC1 complexes protects neurites, we pre-treated striatal neurons with TAT-D2pep or TAT-D2pep-NC prior to addition of quinpirole, followed by immunostaining for MAP-2 to visualize the effect of D2R-DISC1 complexes in neurites.…”

“…However, blockade of striatal D2R by antipsychotic drugs is highly likely to cause side effects, including tardive dyskinesia and obesity (Lally and MacCabe, 2015;Huang et al, 2018). We previously reported that both aripiprazole and haloperidol decrease excessive D2Rdisrupted in schizophrenia 1 (DISC1) complex formation (Zheng et al, 2018). Further, aripiprazole shows better protection of neurite growth than haloperidol in cortical neurons (Zheng et al, 2018).…”

“…We previously reported that both aripiprazole and haloperidol decrease excessive D2Rdisrupted in schizophrenia 1 (DISC1) complex formation (Zheng et al, 2018). Further, aripiprazole shows better protection of neurite growth than haloperidol in cortical neurons (Zheng et al, 2018). However, the role of D2R-DISC1 complexes in spine density and neuronal morphology of striatal neurons is as yet unknown.…”

Disrupted‐in‐schizophrenia 1 functional polymorphisms and D2/D3 receptor availability: A [11C]‐(+)‐PHNO imaging study

“…14 The DISC1-D 2 R complex, which formation is induced by D 2 R stimulation, is involved in the regulation of D 2 R internalisation and downstream behavioural effects of D 2 signalling. 14,15 It has been shown that the DISC1-D 2 R complex inhibits agonist-induced D 2 R internalisation, while its disruption prevents amphetamine-induced locomotor hyperactivity seen in an artificial DISC1 model with a point mutation in exon 2 (Disc1-L100P model). 14 The D 2 R exists in two interconverting states, a low-affinity (μM) state and a high-affinity (nM) state.…”