title: 5-HT7receptor-mediated fear conditioning and possible involvement of extracellular signal-regulated kinase.
abstract: Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The present study examined the involvement of extracellular signal-regulated kinase 1/2 (ERK) signaling on the serotonin (5-HT)7receptor-mediated fear conditioning. Conditioning was performed in a trial in which a tone was followed by an electrical foot-shock. Context- and tone-dependent fear were examined in tests conducted 24 and 48h after conditioning, respectively. The selective 5-HT7receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,-tetrahydrobenzo(c,d)indol-2-(1H)-one (DR4004) (5mg/kg), when administered intraperitoneally (i.p.) immediately after conditioning, caused a significant decrease in both context- and tone-dependent fear responses (freezing behavior). A significant increase in ERK activity was observed in the amygdala of mice that displayed context- or tone-dependent fear responses, and these changes were also inhibited by the administration of DR4004 (5mg/kg, i.p.) immediately after conditioning. In contrast, the increase in hippocampal ERK activity in mice that displayed context-dependent fear responses was further enhanced by the administration of DR4004 (5mg/kg, i.p.). These results suggest that 5-HT7receptor-mediated ERK signaling may play a significant role in the processes of emotional learning and memory.
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: mtsuji@iuhw.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyagawa
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000201:enzymology; D000818:Animals; D003214:Conditioning, Classical; D004644:Emotions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008568:Memory; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: C472242:DR-4004; D007211:Indoles; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 5-HT(7) receptors; Context-dependent fear conditioning; Extracellular signal-regulated kinase; Mouse; Tone-dependent fear conditioning