Phosphodiesterase inhibitors: A novel mechanism for receptor-independent antipsychotic medications

OverviewAll current antipsychotic medications work by binding to Gi-coupled dopamine (DA) D2 receptors. Such medications are thought to affect cellular function primarily by decreasing DA-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP).However, several studies indicate tha...

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Bibliographic Details
Published in:Neuroscience 2004, Vol.129 (1), p.101-107
Main Authors: Maxwell, C.R., Kanes, S.J., Abel, T., Siegel, S.J.
Format: Article
Language:English
Subjects:
amphetamine
Amphetamine - pharmacology
Animals
Antipsychotic Agents - pharmacology
auditory-evoked potential
Biological and medical sciences
Disease Models, Animal
Dopamine - metabolism
Dopamine Agents - pharmacology
Evoked Potentials, Auditory - drug effects
Fundamental and applied biological sciences. Psychology
haloperidol
Medical sciences
Mice
mouse
Neuropharmacology
Pharmacology. Drug treatments
Phosphodiesterase Inhibitors - pharmacology
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
rolipram
Rolipram - pharmacology
schizophrenia
Schizophrenia - physiopathology
Signal Transduction - drug effects
Vertebrates: nervous system and sense organs
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Summary:OverviewAll current antipsychotic medications work by binding to Gi-coupled dopamine (DA) D2 receptors. Such medications are thought to affect cellular function primarily by decreasing DA-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP).However, several studies indicate that cAMP signal transduction abnormalities in schizophrenia may not be limited to D2-containing cells. The current study examines the potential of using non-receptor-based agents that modify intracellular signal transduction as potential antipsychotic medications. MethodsThe indirect DA agonist amphetamine has been used to model the auditory sensory processing deficits in schizophrenia. Such pharmacologically induced abnormalities are reversed by current antipsychotic treatments. This study examines the ability of the phosphodiesterase-4 inhibitor, rolipram, to reverse amphetamine-induced abnormalities in auditory-evoked potentials that are characteristic of schizophrenia. ResultsRolipram reverses amphetamine-induced reductions in auditory-evoked potentials. ConclusionThis finding could lead to novel approaches to receptor-independent treatments for schizophrenia.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2004.07.038