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Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [¹¹C]MP-10 PET rodent imaging study with ex vivo confirmation.
Natesan, S; Ashworth, S; Nielsen, J; Tang, S-P; Salinas, C; Kealey, S; Lauridsen, J B; Stensbøl, T B; Gunn, R N; Rabiner, E A; Kapur, S.
Affiliation
  • Natesan S; Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
  • Ashworth S; Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.
  • Nielsen J; Division of Synaptic Transmission, H. Lundbeck A/S, Copenhagen, Denmark.
  • Tang SP; Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.
  • Salinas C; Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.
  • Kealey S; Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
  • Lauridsen JB; Division of Synaptic Transmission, H. Lundbeck A/S, Copenhagen, Denmark.
  • Stensbøl TB; Division of Synaptic Transmission, H. Lundbeck A/S, Copenhagen, Denmark.
  • Gunn RN; 1] Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK [2] Department of Medicine, Imperial College London, London, UK.
  • Rabiner EA; 1] Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK [2] Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
  • Kapur S; Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
Transl Psychiatry ; 4: e376, 2014 Apr 01.
Article in En | MEDLINE | ID: mdl-24690597
ABSTRACT
A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D2 receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([(11)C]MP-10). The binding of [(11)C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BPND). In rats treated chronically with haloperidol (2 mg kg(-1) per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BPND±s.d. 3.57 ± 0.64 versus 2.86 ± 0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antipsychotic Agents / Neostriatum / Phosphoric Diester Hydrolases / Haloperidol Type of study: Prognostic_studies Limits: Animals Language: En Journal: Transl Psychiatry Year: 2014 Document type: Article Affiliation country: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antipsychotic Agents / Neostriatum / Phosphoric Diester Hydrolases / Haloperidol Type of study: Prognostic_studies Limits: Animals Language: En Journal: Transl Psychiatry Year: 2014 Document type: Article Affiliation country: United kingdom
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