Document Detail

The interaction between dopamine D2-like and beta-adrenergic receptors in the prefrontal cortex is altered by mood-stabilizing agents.
MedLine Citation:
PMID:  16478526     Owner:  NLM     Status:  MEDLINE    
Several studies have suggested the involvement of biogenic monoaminergic neurotransmission in bipolar disorder and in the therapy for this disease. In this study, the effects of the mood-stabilizing drugs lithium, carbamazepine or valproate on the dopaminergic and adrenergic systems, particularly on D2-like and beta-adrenergic receptors, were studied both in cultured rat cortical neurones and in rat prefrontal cortex. In vitro and in vivo data showed that stimulation of beta-adrenergic receptors with isoproterenol increased cyclic adenosine monophosphate (cAMP) levels and this effect was significantly inhibited by lithium, carbamazepine or valproate. The activation of dopamine D2-like receptors with quinpirole decreased the isoproterenol-induced rise in cAMP in control conditions. This inhibition was observed in vivo after chronic treatment of the rats with carbamazepine or valproate, but not after treatment with lithium or in cultured rat cortical neurones after 48 h exposure to the three mood stabilizers. Dopamine D2 and beta1-adrenergic receptors were found to be co-localized in prefrontal cortical cells, as determined by immunohistochemistry, but western blot experiments revealed that receptor levels were differentially affected by treatment with the three mood stabilizers. These data show that mood stabilizers affect D2 receptor-mediated regulation of beta-adrenergic signalling and that each drug acts by a unique mechanism.
Liliana P Montezinho; M Margarida C A Castro; Carlos B Duarte; Silke Penschuck; Carlos F G C Geraldes; Arne Mørk
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  96     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-15     Completed Date:  2006-05-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1336-48     Citation Subset:  IM    
Department of Biochemistry, Faculty of Science and Technoloigy, University of Coimbra, Portugal.
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MeSH Terms
Adrenergic beta-Agonists / pharmacology
Antimanic Agents / pharmacology*
Blotting, Western / methods
Cells, Cultured
Cyclic AMP / metabolism
Dopamine Agonists / pharmacology
Drug Interactions
Gene Expression Regulation / drug effects
Immunohistochemistry / methods
Isoproterenol / pharmacology
Microdialysis / methods
Neurons / drug effects*
Prefrontal Cortex / cytology*
Quinpirole / pharmacology
Radioimmunoassay / methods
Rats, Wistar
Receptors, Adrenergic, beta / metabolism*
Receptors, Dopamine D2 / metabolism*
Time Factors
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Antimanic Agents; 0/Dopamine Agonists; 0/Receptors, Adrenergic, beta; 0/Receptors, Dopamine D2; 60-92-4/Cyclic AMP; 7683-59-2/Isoproterenol; 85760-74-3/Quinpirole

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