Preclinical molecular imaging of glutamatergic and dopaminergic neuroreceptor kinetics in obsessive compulsive disorder

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Abstract

Background:

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.

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