The interaction between dopamine D2-like and beta-adrenergic receptors in the prefrontal cortex is altered by mood-stabilizing agents.
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.
Montezinho
Liliana P
LP
Department of Biochemistry, Faculty of Science and Technoloigy, University of Coimbra, Portugal.
Castro
M Margarida C A
MM
Duarte
Carlos B
CB
Penschuck
Silke
S
Geraldes
Carlos F G C
CF
Mørk
Arne
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000166:cytology*; D019257:Quinpirole / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018692:Antimanic Agents; D018491:Dopamine Agonists; D011943:Receptors, Adrenergic, beta; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000242:Cyclic AMP; D007545:Isoproterenol