Repeated antidepressant therapy increases cyclic GMP signaling in rat hippocampus.
Cyclic adenosine monophosphpate (cAMP) signaling is thought to be involved in the pathophysiology of major depressive disorder and antidepressant action; however, relatively little is known about the possible role of cyclic guanosine monophosphate (cGMP) signaling. Accumulating evidence suggests that crosstalk occurs between cAMP and cGMP pathways. There is a need to clarify the trajectory of cAMP and cGMP concentrations, their synthesis by cyclases, and degradation by phosphodiesterases (PDEs) to understand the role of cyclic mononucleotide signaling in the effect of chronic antidepressant therapy. We used quantitative real-time PCR and enzyme immunoassay to systematically investigate the expression of intracellular signaling cascade elements in the hippocampus of rats chronically treated with the antidepressants fluoxetine and amitriptyline. We found increased cGMP levels, which were consistent with our findings of decreased PDE gene expression. Immunoassay results showed unchanged cAMP levels. We conclude that increased cGMP signaling might underlie the efficacy of chronic antidepressant treatment.
Center on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, 1580 NW 10th Avenue, Miami, FL 33136, USA.
Gillian W
GW
Reierson
Claudio A
CA
Mastronardi
Julio
J
Licinio
Ma-Li
ML
Wong
D000262:Adenylyl Cyclases / Q000096:biosynthesis; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D000928:Antidepressive Agents; D007527:Isoenzymes; D005473:Fluoxetine; D000639:Amitriptyline; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C100622:adenylyl cyclase 2; D006152:Cyclic GMP