Ecto-nucleotidase pathway is altered by different treatments with fluoxetine and nortriptyline

• Published in: European journal of pharmacology Vol. 583; no. 1; pp. 18 - 25
• Main Authors: Pedrazza, Eduardo Luiz, Rico, Eduardo Pacheco, Senger, Mario Roberto, Pedrazza, Leonardo, Zimmermann, Fernanda Francine, Sarkis, João José Freitas, Bogo, Maurício Reis, Bonan, Carla Denise
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 31.03.2008; Elsevier
• Subjects: Adenosine - metabolism; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Adult and adolescent clinical studies; Animals; Antidepressive Agents, Second-Generation - pharmacology; Antidepressive Agents, Tricyclic - pharmacology; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Depression; Ecto-5′-nucleotidase; Ecto-nucleotidase; Extracellular Space - drug effects; Extracellular Space - metabolism; Fluoxetine; Fluoxetine - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Isoenzymes - metabolism; Male; Medical sciences; Mood disorders; Norepinephrine - metabolism; Nortriptyline; Nortriptyline - pharmacology; NTPDase; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Serotonin - metabolism; Signal Transduction - drug effects; Synaptosomes - drug effects; Synaptosomes - metabolism; Nortriptyline; Ecto-nucleotidase; Depression; Ecto-5′-nucleotidase; Fluoxetine; NTPDase; Mood disorder; Nucleotidase; Serotonin; 5'-Nucleotidase; Enzyme; Psychotropic; Phosphoric monoester hydrolases; Esterases; Tricyclic compound; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Treatment; Neurotransmitter; Hydrolases; Antidepressant agent; Ecto-5'-nucleotidase
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.01.013

Depression is one of the most disabling diseases and causes a significant burden to both individual and society. Selective serotonin reuptake inhibitors and tricyclic antidepressants, such as fluoxetine and nortriptyline, respectively, are commonly used in treatment for depression. These antidepressants were tested on cerebral cortex and hippocampal synaptosomes after acute and chronic in vivo and in vitro treatments. In chronic treatment, fluoxetine and nortriptyline decreased ATP hydrolysis (17.8% and 16.3%, respectively) in hippocampus. In cerebral cortex, nortriptyline increased ATP (32.3%), ADP (51.8%), and AMP (59.5%) hydrolysis. However, fluoxetine decreased ATP (25.5%) hydrolysis and increased ADP (80.1%) and AMP (33.3%) hydrolysis. Significant activation of ADP hydrolysis was also observed in acute treatment with nortriptyline (49.8%) in cerebral cortex. However, in hippocampus, ATP (24.7%) and ADP (46.1%) hydrolysis were inhibited. Fluoxetine did not alter enzyme activities in acute treatment for both structures. In addition, there were significant changes in NTPDase activities when fluoxetine and nortriptyline (100, 250, and 500 µM) were tested in vitro. There was no inhibitory effect of fluoxetine and nortriptyline on AMP hydrolysis in cerebral cortex and hippocampus. The findings showed that these antidepressant drugs can affect the ecto-nucleotidase pathway, suggesting that the extracellular adenosine levels could be modulated by these drugs.