Differential effects of within-day continuous vs. transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Peter TurroneJosé N Nobrega

Abstract

Accumulating evidence suggests that antipsychotics (APs) that lead to sustained blockade of dopamine D(2) receptors are more likely to induce acute extrapyramidal side effects (EPS) compared to APs that only occupy D(2) receptors transiently. It is unclear, however, whether a similar relationship exists for long-term AP-induced motoric side effects like tardive dyskinesia (TD). The objective of this study was to ascertain whether transient (via daily subcutaneous (s.c.) injections) vs continuous (via osmotic minipump) AP-induced D(2) receptor occupancy differentially affects the development of haloperidol-induced vacuous chewing movements (VCMs), an animal model of TD. Six groups of 12 rats received 0.1, 0.25, or 1 mg/kg of haloperidol or vehicle (n=36) via osmotic minipump (to provide within-day sustained) or daily s.c. injection (within-day transient) for 8 weeks. VCMs were measured on a weekly basis and D(2) occupancy levels were measured in vivo using [(3)H]-raclopride at the end of the experiment. Minipump-treated rats developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (57%), 0.25 mg/kg/day (70%), and 1 mg/kg/day (88%). S.C.-treated rats also developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (83% p...Continue Reading

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Citations

Aug 9, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nathalie GinovartShitij Kapur
Jul 24, 2010·Schizophrenia Bulletin·Gary Remington, Shitij Kapur
Mar 13, 2012·Behavioral and Brain Functions : BBF·Pierre J BlanchetDaniel Lévesque
Feb 26, 2008·Biological Psychiatry·Anne-Noël SamahaShitij Kapur
Mar 14, 2016·Schizophrenia Research·Vilte E BarakauskasWilliam G Honer
Feb 12, 2005·Biological Psychiatry·Peter TurroneJosé N Nobrega
Feb 28, 2006·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·M SaldañaC Marin
Dec 6, 2005·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Rossella MedoriGerhard Gründer
Aug 16, 2011·Pharmacology, Biochemistry, and Behavior·Gary RemingtonSridhar Natesan
Aug 28, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Joshua ListerGary Remington
Oct 1, 2018·The European Journal of Neuroscience·T Celeste Napier, Amanda L Persons
Jul 29, 2017·Expert Review of Neurotherapeutics·Haitham SalemAntonio L Teixeira
Dec 22, 2020·Behavioural Brain Research·Alice ServonnetAnne-Noël Samaha

Related Concepts

Dose-Response Relationship, Drug
Haldol
Chewing
Plasma Protein Binding Capacity
Medication Systems, Programmable Implantable
Rats, Holtzman
Dopamine D2 Receptor
Dopamine D2 Receptor Antagonists

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