Preclinical molecular imaging of glutamatergic and dopaminergic neuroreceptor kinetics in obsessive compulsive disorder
Molecular neuroimaging was applied in the quinpirole rat model for compulsive checking in OCD to visualize the D2- and mGluR5-receptor occupancy with Raclopride and ABP-688 microPET/CT.Methods:
Animals (n = 48) were exposed to either saline (CTRL; 1 mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5 mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7 weeks (chronic group). Animals underwent PET/CT after the 1st injection (acute) or before initial exposure and following the 10th injection in week 5 (chronic). For the latter, each injection was paired with an open field test and video tracking.Results:
The QP animals displayed a strong increase in visiting frequency (checking) in the chronic group (+ 699.29%) compared to the control animals. Acute administration of the drug caused significant (p < 0.01) decreases in D2R occupancy in the CP (− 42.03% ± 4.01%). Chronical exposure resulted in significantly stronger decreases in the CP (− 52.29% ± 3.79%). Furthermore significant increases in mGluR5 occupancy were found in the CP (10.36% ± 4.09%), anterior cingulate cortex (13.26% ± 4.01%), amygdala (24.36% ± 6.86%), entorhinal cortex (18.49% ± 5.14%) and nucleus accumbens (13.8% ± 4.87%) of the chronic group, not present after acute exposure.Conclusions:
Compared to acute exposure, sensitisation to QP as a model for OCD differs both on a dopaminergic and glutamateric level, indicating involvement of processes such as receptor internalization and changes in extracellular availability of both neurotransmitters.