title: Enhanced extinction of contextual fear conditioning in ClockΔ19 mutant mice.
abstract: Clock genes have been implicated in several disorders, such as schizophrenia, bipolar disorder, autism spectrum disorders, and drug dependence. However, few studies to date have examined the role of clock genes in fear-related behaviors. The authors used mice with the ClockΔ19 mutation to assess the involvement of this gene in contextual fear conditioning. Male wild-type (WT) and ClockΔ19 mutant mice underwent a single session of contextual fear conditioning (12 min, 4 unsignaled shocks), followed by daily 12-min retention trials. There were no differences between mutant and WT mice in the acquisition of contextual fear, and WT and mutant mice demonstrated similar freezing during the first retention session. However, extinction of contextual fear was accelerated in mutant mice across the remaining retention sessions, as compared to WT mice, suggesting a role for Clock in extinction following aversive learning. Because the ClockΔ19 mutation has previously been demonstrated to result in an increase in dopamine signaling, the authors confirmed the role of dopamine in extinction learning using preretention session administration of a low dose of the dopamine transport reuptake inhibitor modafinil (0.75 mg/kg), which resulted in decreased freezing across retention sessions. These findings are consistent with an emerging portrayal of the importance of Clock genes in noncircadian functions, as well as the important role of dopamine in extinction learning.
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health.
authors.forename: Rick E
authors.initials: RE
authors.lastname: Bernardi
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D056926:CLOCK Proteins / Q000235:genetics / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000077408:Modafinil; D009043:Motor Activity / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D018765:Dopamine Uptake Inhibitors; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D000077408:Modafinil