Document Detail

Cocaine modulates pathways for photic and nonphotic entrainment of the mammalian SCN circadian clock.
MedLine Citation:
PMID:  22218419     Owner:  NLM     Status:  MEDLINE    
Cocaine abuse is highly disruptive to circadian physiological and behavioral rhythms. The present study was undertaken to determine whether such effects are manifest through actions on critical photic and nonphotic regulatory pathways in the master circadian clock of the mouse suprachiasmatic nucleus (SCN). Impairment of SCN photic signaling by systemic (intraperitoneal) cocaine injection was evidenced by strong (60%) attenuation of light-induced phase-delay shifts of circadian locomotor activity during the early night. A nonphotic action of cocaine was apparent from its induction of 1-h circadian phase-advance shifts at midday. The serotonin receptor antagonist, metergoline, blocked shifting by 80%, implicating a serotonergic mechanism. Reverse microdialysis perfusion of the SCN with cocaine at midday induced 3.7 h phase-advance shifts. Control perfusions with lidocaine and artificial cerebrospinal fluid had little shifting effect. In complementary in vitro experiments, photic-like phase-delay shifts of the SCN circadian neuronal activity rhythm induced by glutamate application to the SCN were completely blocked by cocaine. Cocaine treatment of SCN slices alone at subjective midday, but not the subjective night, induced 3-h phase-advance shifts. Lidocaine had no shifting effect. Cocaine-induced phase shifts were completely blocked by metergoline, but not by the dopamine receptor antagonist, fluphenazine. Finally, pretreatment of SCN slices for 2 h with a low concentration of serotonin agonist (to block subsequent serotonergic phase resetting) abolished cocaine-induced phase shifts at subjective midday. These results reveal multiple effects of cocaine on adult circadian clock regulation that are registered within the SCN and involve enhanced serotonergic transmission.
J David Glass; Allison J Brager; Adam C Stowie; Rebecca A Prosser
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Publication Detail:
Type:  Journal Article     Date:  2012-01-04
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  302     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-16     Completed Date:  2012-05-15     Revised Date:  2012-05-23    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R740-50     Citation Subset:  IM    
Department of Biological Sciences, Kent State Univ., Kent, OH 44242, USA.
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MeSH Terms
Circadian Clocks / drug effects*,  physiology
Cocaine / pharmacology*
Dopamine Uptake Inhibitors / pharmacology
Fluphenazine / pharmacology
Lidocaine / pharmacology
Metergoline / pharmacology
Mice, Inbred C57BL
Models, Animal
Motor Activity / drug effects
Photic Stimulation*
Serotonin Receptor Agonists / pharmacology
Signal Transduction / drug effects*,  physiology
Suprachiasmatic Nucleus / drug effects*,  physiology
Reg. No./Substance:
0/Dopamine Uptake Inhibitors; 0/Serotonin Receptor Agonists; 137-58-6/Lidocaine; 17692-51-2/Metergoline; 50-36-2/Cocaine; 69-23-8/Fluphenazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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