Effects of mood stabilizers on the inhibition of adenylate cyclase via dopamine D2-like receptors
Correction(s) for this article
-
Erratum
- Volume 9Issue 5Bipolar Disorders
- pages: 549-549
- First Published online: August 2, 2007
Liliana P Montezinho
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorArne Mørk
Department of Neurochemistry, H. Lundbeck A/S, Valby, Denmark
Search for more papers by this authorCarlos B Duarte
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Department of Zoology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorSilke Penschuck
Department of Neuropharmacology, H. Lundbeck A/S, Valby, Denmark
Search for more papers by this authorCarlos FGC Geraldes
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorM Margarida CA Castro
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorLiliana P Montezinho
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorArne Mørk
Department of Neurochemistry, H. Lundbeck A/S, Valby, Denmark
Search for more papers by this authorCarlos B Duarte
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Department of Zoology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorSilke Penschuck
Department of Neuropharmacology, H. Lundbeck A/S, Valby, Denmark
Search for more papers by this authorCarlos FGC Geraldes
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorM Margarida CA Castro
Department of Biochemistry
NMR Centre
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorThe authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
Abstract
Objective: The mood stabilizing drugs lithium, carbamazepine and valproate modulate brain adenosine monophosphate (cAMP) levels, which are assumed to be elevated in bipolar disorder patients. The aim of this work was to investigate how these three mood stabilizing agents affect the regulation of cAMP levels by dopamine D2-like receptors in vitro in rat cortical neurons in culture and in vivo in the rat prefrontal cortex.
Methods: The production of cAMP was measured in the cultured cortical neurons or in microdialysis samples collected from the prefrontal cortex of freely moving rats using the [8-3H] and [125I] radioimmunoassay kits.
Results: In vitro and in vivo data showed that the treatment with the mood stabilizing drugs had no effect on basal cAMP levels in vitro, but had differential effects in vivo. Direct stimulation of adenylate cyclase (AC) with forskolin increased cAMP levels both in vitro and in vivo, and this effect was significantly inhibited by all three mood stabilizers. Activation of dopamine D2-like receptors with quinpirole partially inhibited forskolin-induced increase in cAMP in untreated cultures, but no effect was observed in cortical neuron cultures treated with the mood stabilizing drugs. Similar results were obtained by chronic treatment with lithium and valproate in the prefrontal cortex in vivo. However, surprisingly, in carbamazepine-treated rats the activation of dopamine D2-like receptors enhanced the responsiveness of AC to subsequent activation by forskolin, possibly as a consequence of chronic inhibition of the activity of the enzyme.
Conclusions: It was shown that each of these drugs affects basal- and forskolin-evoked cAMP levels in a distinct way, resulting in differential responses to dopamine D2-like receptors activation.
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