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

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.