S Servaes1, D Glorie2, J Verhaeghe3, S Stroobants4, S Staelens5. 1. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: stijn.servaes@uantwerpen.be. 2. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: dorien.glorie@uantwerpen.be. 3. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: jeroen.verhaeghe@uantwerpen.be. 4. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium; Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium. Electronic address: sigrid.stroobants@uza.be. 5. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: steven.staelens@uantwerpen.be.
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; 1mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7weeks (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.
BACKGROUND: Molecular neuroimaging was applied in the quinpirolerat 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; 1mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7weeks (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.
Authors: Pino Alonso; Raquel Rabionet; Laura Domènech; Jesse Willis; Maria Alemany-Navarro; Marta Morell; Eva Real; Geòrgia Escaramís; Sara Bertolín; Daniel Sánchez Chinchilla; Susanna Balcells; Cinto Segalàs; Xavier Estivill; Jose M Menchón; Toni Gabaldón Journal: Sci Rep Date: 2022-01-27 Impact factor: 4.379