Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [18F]JNJ42259152 PET study in rats

Purpose Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neur...

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Bibliographic Details
Published in:European journal of nuclear medicine and molecular imaging 2022, Vol.49 (2), p.492-502
Main Authors: de Laat, Bart, Kling, Yvonne E., Schroyen, Gwen, Ooms, Maarten, Hooker, Jacob M., Bormans, Guy, Van Laere, Koen, Ceccarini, Jenny
Format: Article
Language:English
Subjects:
Alcohol Drinking - adverse effects
Alcohol use
Alcoholism - diagnostic imaging
Alcoholism - metabolism
Animals
Anxiety
Availability
Binding
Brain - diagnostic imaging
Brain - metabolism
Cardiology
Caudate-putamen
Cerebellum
Decision analysis
Decision making
Disorders
Dopamine
Exposure
Field tests
Gambling
Gene expression
Globus pallidus
Imaging
In vivo methods and tests
Medicine
Medicine & Public Health
Mental disorders
Neostriatum
Nuclear Medicine
Nucleus accumbens
Oncology
Open-field behavior
Original Article
Orthopedics
Phosphodiesterase
Phosphoric Diester Hydrolases - metabolism
Positron emission tomography
Positron-Emission Tomography - methods
Putamen
Pyrazoles
Pyridines
Radiology
Rats
Risk analysis
Risk factors
Spiny neurons
Substrates
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Summary:Purpose Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety. Methods We performed a longitudinal [ 18 F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6 weeks of alcohol exposure, 2 weeks of abstinence followed by 1 week relapse. Parametric PDE10A-binding potential (BP ND ) images were generated using a Logan reference tissue model with cerebellum as reference region and were analyzed using both a volume-of-interest and voxel-based approach. Moreover, individual decision-making and anxiety levels were assessed with the rat Iowa Gambling Task and open-field test over the IAE model. Results We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2 weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A-binding potential after 2 versus 4 weeks of exposure showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens ( p FWE-corrected  
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-021-05448-3