title: Preclinical molecular imaging of glutamatergic and dopaminergic neuroreceptor kinetics in obsessive compulsive disorder.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: stijn.servaes@uantwerpen.be.
authors.forename: S
authors.initials: S
authors.lastname: Servaes
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: dorien.glorie@uantwerpen.be.
authors.forename: D
authors.initials: D
authors.lastname: Glorie
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: jeroen.verhaeghe@uantwerpen.be.
authors.forename: J
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Stroobants
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: steven.staelens@uantwerpen.be.
authors.forename: S
authors.initials: S
authors.lastname: Staelens
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D059333:Central Nervous System Sensitization / Q000187:drug effects; D059907:Functional Neuroimaging; D007700:Kinetics; D008297:Male; D057054:Molecular Imaging; D009043:Motor Activity / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism*; D010091:Oximes / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D013997:Time Factors
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578937:Grm5 protein, rat; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D019257:Quinpirole
keywords: Dopamine; Glutamate; MicroPET; OCD; Preclinical