Molecular neuroscienceEffect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum
Section snippets
Experimental procedures
C3H/HeJ mice (n=72), 8 weeks old and weighing 25–30g were purchased from Jackson Laboratory (Bar Harbor, ME, USA). Animals were housed in groups of three and had free access to laboratory chow and water except during behavioral experiments. They were kept in a temperature-controlled room under conditions of 14 h light: 10 h dark cycle (lights on at 5:00 am; ZT00). The experimental protocol was approved by the Institutional Animal Care and Ethics Committee.
Results
Repeated injections (14 days) of fluoxetine or cocaine significantly increased AANAT mRNA in all brain areas tested (measured 24 h after the last injection) whereas a single injection of these drugs did not cause any lasting changes in AANAT expression levels (Fig. 2). In contrast, fluoxetine and cocaine treatments caused different lasting effects on expression patterns in the clock genes tested depending on the drug, treatment schedule of the drugs, and the region studied.
Overall, fluoxetine
Discussion
In this study we found a remarkable delayed up-regulation in the expression of brain AANAT after the repeated administration of either fluoxetine or cocaine. This is to say that compared with vehicle-injected controls, 24 h after 14 days of treatments the drug-injected mice had elevated AANAT mRNA levels. The effect of fluoxetine was slightly greater in the hippocampus and the cortex whereas the effect of cocaine was greater in the striatum. Although AANAT is primarily considered for its role
Conclusion
Using a repeated drug administration model for either fluoxetine or cocaine, we have characterized a region- and drug-specific expression of clock genes. Our results suggest that clock genes and the mechanisms regulating these genes may participate in the long-term changes caused by psychoactive drugs. Since these genes have the potential to regulate a second group of genes (i.e. clock-controlled genes) with E-box motifs in their promoter, region-dependent lasting alteration of clock genes by
Acknowledgments
This research was supported by NIH grants R01 DA15072 (T.U.) and R01 MH61572 (H.M.).
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