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

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.

Jaar van publicatie:2017

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:2

CSS-citation score:1

Authors from:Higher Education

Toegankelijkheid:Closed