Lack of neurotensin type 1 receptor facilitates contextual fear memory depending on the memory strength

• Published in: Pharmacology, biochemistry and behavior Vol. 96; no. 3; pp. 363 - 369
• Main Authors: Yamada, Daisuke, Wada, Etsuko, Amano, Taiju, Wada, Keiji, Sekiguchi, Masayuki
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.09.2010; Elsevier
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Biological and medical sciences; Conditioning, Classical - physiology; Dizocilpine Maleate - pharmacology; Electroshock; Excitatory Amino Acid Antagonists - pharmacology; Extinction, Psychological; Fear - psychology; Fear conditioning; Fear memory; Freezing Reaction, Cataleptic - physiology; Knockout mouse; Medical sciences; Memory - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Neurotensin receptor type 1; Propranolol - pharmacology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, Neurotensin - agonists; Receptors, Neurotensin - genetics; Receptors, Neurotensin - physiology; Reconsolidation; Fear memory; Reconsolidation; Neurotensin receptor type 1; Knockout mouse; Context; Fear; Neurotensin receptor; Memory; Emotion emotionality
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2010.06.007

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 3 min to the context 24 and 48 h 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 β-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.