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Title
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Preclinical molecular imaging of glutamatergic and dopaminergic neuroreceptor kinetics in obsessive compulsive disorder
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Progress in neuro-psychopharmacology and biological psychiatry. - Oxford
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Publication
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Oxford
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2017
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ISSN
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0278-5846
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DOI
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10.1016/J.PNPBP.2017.02.027
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Volume/pages
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77
(2017)
, p. 90-98
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ISI
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000404308100011
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Pubmed ID
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28365375
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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