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Pharmacological MRI as a Molecular Imaging Technique
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Y. Iris Chen, Bruce G. Jenkins
Second, even if a DAR-specific PET ligand is available, the receptor-binding technique again only provides static information, such as the availability or receptor density of DAR. However, the degree of dopamine release can be estimated using a displacement approach67–70 in which the endogenous dopamine competes with the radiolabeled ligands — greater reduction of the measured binding potential indicates a greater degree of dopamine release (more radiolabeled ligands have been displaced by the endogenous dopamine). The DAR function can also be probed by using phMRI.71 Although there is no DAR-specific ligand, most of the D2 ligands have greater affinity to DAR than to the postsynaptic D2 receptor.72–77 In other words, a low behavioral dose of a D2 ligand acts mostly on the presynaptic DAR rather than on the postsynaptic D2 receptor. Evidence of the dose-dependent hemodynamic changes of the D2 ligands was shown in Chen et al.,71 reporting that a higher dose of eticlopride decreased rCBV in the caudate/putamen (CPu) and nucleus accumbens (NAc), while a lower dose of eticlopride induced rCBV increases in those areas (Figure 12.6). When operating at low dose range, a D2 antagonist such as eticlopride will enhance the amphetamine-induced dopamine release in a dose-dependent manner. Indeed, at a low behavioral dose range, eticlopride potentiated the AMPH-induced dopamine release, and hence we observed a potentiation of the corresponding rCBV increase in a dose-dependent manner (see Figure 12.6 and Chen et al.71). Since the DAR function may be altered in various disorders, including cocaine addiction and schizophrenia, the phMRI measured dose-response curve of the DAR function can help to evaluate the status of the dopaminergic system, and thus the efficacy to a specific therapy.
Involvement of D2 receptor in the NAc in chronic unpredictable stress-induced depression-like behaviors
Published in Stress, 2020
Hui Qiao, Sha Yang, Chang Xu, Xin-Ming Ma, Shu-Cheng An
We suspected that (1) stress induced a significant reduction of the DA levels in the NAc and weakened D2R signaling pathways. Meanwhile, D2R expression was significantly decreased after CUS to compensate for the change in the DA level. A weakened D2R signaling pathway leads to helplessness (i.e. longer immobility time). (2) Activation of presynaptic D2R by quinpirole directly inhibits DA release through negative feedback regulation, which affects both tonic and phasic release according to previous study (Escobar et al., 2015). Quinpirole, of course, may activate postsynaptic D2Rs either, while the presynaptic pathway is a primary pathway affected. (3) Eticlopride inhibits D2Rs, which increase the DA level via the presynaptic pathway, and reverses the depressive behaviors induced by CUS (Figure 4). Previous studies show that pretreatment with eticlopride attenuates the dopaminergic deficits induced by methamphetamine through delaying the formation of dopamine transporter complexes, increasing vesicular monoamine transporter 2 immunoreactivity, and inhibiting astrocytic activation (Hadlock, Chu, Walters, Hanson, & Fleckenstein, 2010).