Striatal phosphodiesterase 10A availability is altered secondary to chronic changes in dopamine neurotransmission.

ABSTRACT: Background:Phosphodiesterase 10A (PDE10A) is an important regulator of nigrostriatal dopamine (DA) neurotransmission. However, little is known on the effect of alterations in DA neurotransmission on PDE10A availability. Here, we used [18F]JNJ42259152 PET to measure changes in PDE10A availability, secondary to pharmacological alterations in DA release and to investigate whether these are D1- or D2-receptor driven. Results:Acute treatment of rats using D-amphetamine (5 mg, s.c. and 1 mg/kg i.v.) did not result in a significant change in PDE10A BPND compared to baseline conditions. 5-day D-amphetamine treatment (5 mg/kg, s.c.) increased striatal PDE10A BPND compared to the baseline (+24 %, p?=?0.03). Treatment with the selective D2 antagonist SCH23390 (1 mg/kg) and D-amphetamine decreased PDE10A binding (-22 %, p?=?0.03). Treatment with only SCH23390 further decreased PDE10A binding (-26 %, p?=?0.03). No significant alterations in PDE10A mRNA levels were observed. Conclusions:Repeated D-amphetamine treatment significantly increased PDE10A binding, which is not observed upon selective D1 receptor blocking. This study suggests a potential pharmacological interaction between PDE10A enzymes and drugs modifying DA neurotransmission. Therefore, PDE10A binding in patients with neuropsychiatric disorders might be modulated by chronic DA-related treatment.

SUBMITTER: Ooms M 

PROVIDER: S-EPMC5843803 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature