title: Lack of neurotensin type 1 receptor facilitates contextual fear memory depending on the memory strength.
abstract: Neurotensin is known to have antipsychotic-like behavioral and neurochemical effects, but its participation in fear memory has not been fully elucidated. Here, we report that a lack of type 1 neurotensin receptor (Ntsr1) increases the behavioral fear response elicited by weak fear memory. Adult Ntsr1-knockout (KO) mice and their wild-type (WT) littermates were compared in contextual fear conditioning. The mice were exposed twice for 3min to the context 24 and 48h after conditioning (first and second exposure, respectively), and freezing response of mice at the exposure was measured to evaluate fear memory. Ntsr1-KO mice showed a higher freezing rate than WT mice at both first and second exposures under the condition where a relatively weak unconditioned stimulus (footshock) was applied and thus elicited a relatively lower freezing rate. The difference in the first exposure between Ntsr1-KO and WT mice disappeared under the condition where a more intense unconditioned stimulus was used. The enhancement of freezing response in Ntsr1-KO mice at second exposure was abolished by propranolol, a beta-adrenergic blocker that suppresses fear memory reconsolidation, and suppressed by MK-801, an NMDA receptor antagonist. These results suggest that Ntsr1 plays inhibitory roles in weak fear memory.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Etsuko
authors.initials: E
authors.lastname: Wada
authors.forename: Taiju
authors.initials: T
authors.lastname: Amano
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological; D005239:Fear / Q000523:psychology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D018028:Receptors, Neurotensin / Q000819:agonists / Q000235:genetics / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D016291:Dizocilpine Maleate; D011433:Propranolol