Format

Send to

Choose Destination
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 3;77:90-98. doi: 10.1016/j.pnpbp.2017.02.027. Epub 2017 Mar 30.

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

Author information

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.

KEYWORDS:

Dopamine; Glutamate; MicroPET; OCD; Preclinical

PMID:
28365375
DOI:
10.1016/j.pnpbp.2017.02.027
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center