Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum

• Published in: Neuroscience Vol. 134; no. 4; pp. 1309 - 1316
• Main Authors: Uz, T., Ahmed, R., Akhisaroglu, M., Kurtuncu, M., Imbesi, M., Dirim Arslan, A., Manev, H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: addiction; Animals; Antidepressive Agents, Second-Generation - pharmacology; Arylalkylamine N-Acetyltransferase - drug effects; Arylalkylamine N-Acetyltransferase - metabolism; Behavior, Addictive - genetics; Behavior, Addictive - physiopathology; Biological and medical sciences; Brain - drug effects; CLOCK Proteins; Cocaine - pharmacology; Corpus Striatum - drug effects; depression; Depression - genetics; Depression - physiopathology; Dopamine Uptake Inhibitors - pharmacology; Fluoxetine - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; hippocampus; Hippocampus - drug effects; Medical sciences; Mice; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reverse Transcriptase Polymerase Chain Reaction; striatum; Time Factors; Trans-Activators - drug effects; Trans-Activators - genetics; transcription factors; Vertebrates: nervous system and sense organs; RT; hippocampus; transcription factors; DMSO; addiction; cyc; NPAS2; AANAT; striatum; RT-PCR; ZT; depression; SCN; CNS stimulant; Psychotropic; Fluoxetine; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Gene expression; Encephalon; Vertebrata; Mammalia; Mouse; Animal; Cocaine; Drug of abuse; Transcription factor; Hippocampus
• DOI: 10.1016/j.neuroscience.2005.05.003
• ISSN: 0306-4522

Long-term drug-induced alterations in CNS gene expression may be responsible for some therapeutic effects, such as antidepressant action, as well as for psychopathological conditions, such as drug addiction and abuse. Transcription factors called “clock” genes can be affected by psychotropic drugs and may modify the expression pattern of other genes. In this study in mice, we investigated the delayed effects of single and repeated (i.e. 14 days) administration of the antidepressant fluoxetine and the psychostimulant cocaine on the brain expression of clock genes Period1, Period2, Period3, Clock, Bmal1, Cryptochrome1, Cryptochrome2, and NPAS2 (neuronal PAS domain protein 2), and their putative target gene, serotonin N-acetyltransferase. Mice were treated at ZT05 (lights on at 5:00 am; ZT00). Brain samples (i.e. hippocampus, striatum, and prefrontal cortex) were processed for a semi-quantitative mRNA assay. Repeated but not single treatment with either drug increased serotonin N-acetyltransferase expression in all areas tested. On the other hand, the expression of clock genes was differentially affected depending on the drug (i.e. fluoxetine and cocaine), treatment schedule (i.e. single and repeated), and brain area (i.e. hippocampus and striatum) tested. More pronounced changes were induced by repeated rather than single administrations of fluoxetine or cocaine. We propose that the effects of psychoactive drugs on clock transcription factors may mediate long-term drug-induced changes, possibly by regulating the expression of a second set of genes (i.e. clock-controlled genes).