Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. 2006

Jeffrey Sprouse, and John Braselton, and Linda Reynolds
Department of Neuroscience, Pfizer Global Research & Development, Groton, Connecticut 06340, USA. jeffrey.s.sprouse@pfizer.com

BACKGROUND The documented ability of serotonin (5-HT) to directly modulate circadian rhythms prompted interest in a similar role for therapeutic agents that readily enhance 5-HT neurotransmission, namely the selective serotonin reuptake inhibitors (SSRIs). METHODS Extracellular recordings of unit firing of suprachiasmatic nucleus (SCN) neurons maintained in slice culture enabled determinations of circadian rhythmicity. Shifts in the peak of activity were determined during the next circadian cycle following drug exposure. RESULTS Fluoxetine (10 microm, 60 minutes incubation) produced robust phase advances only in the presence of L-tryptophan (.5 microm), added to maintain serotonergic tone. CONCLUSIONS Actions of SSRIs at the level of the circadian biological clock add to the list of pharmacological effects for this drug class and encourage speculation as to their importance clinically.

UI MeSH Term Description Entries
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005473 Fluoxetine The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Fluoxetin,Fluoxetine Hydrochloride,Lilly-110140,N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine,Prozac,Sarafem,Lilly 110140,Lilly110140
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013493 Suprachiasmatic Nucleus An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the OPTIC CHIASM. Hypothalamic Suprachiasmatic Nuclei,Hypothalamic Suprachiasmatic Nucleus,Suprachiasmatic Nuclei,Suprachiasmatic Nuclei, Hypothalamic,Suprachiasmatic Nucleus, Hypothalamic
D014364 Tryptophan An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. Ardeydorm,Ardeytropin,L-Tryptophan,L-Tryptophan-ratiopharm,Levotryptophan,Lyphan,Naturruhe,Optimax,PMS-Tryptophan,Trofan,Tryptacin,Tryptan,Tryptophan Metabolism Alterations,ratio-Tryptophan,L Tryptophan,L Tryptophan ratiopharm,PMS Tryptophan,ratio Tryptophan

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