Investigating the effect of bilateral amygdala lesions on fear conditioning and social interaction in the male Mongolian gerbil

Identification of the selective neurokinin NK1 receptor antagonist, 2-(R)-(1-(R)-3,5-Bis(trifluromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-oxo-1,2,4-triazol-5yl)methylmor-phine (MK-869), as a novel therapeutic approach for anxiety/depression has led to increased use of the Mongolian gerbil in behavioural studies since the gerbil NK1 receptor pharmacology is similar to human, but not rat or mouse. Within this species, foot tapping and immobility elicited by aversive conditioning, as well as social interaction have been shown to be sensitive to clinically used anxiolytic and antidepressant agents and also NK1 receptor antagonists. The high levels of NK1 receptor binding in the amygdala as well as preclinical studies demonstrating increased release of substance P and corresponding internalisation of NK1 receptors in the basolateral amygdala in response to stressful stimuli suggest that the BLA may represent a potential site of action for NK1 receptor antagonists in anxiety and/or depression. Therefore, in the current study, we assessed the effect of bilateral BLA lesions in male Mongolian gerbils on footshock-induced foot tapping and immobility, social interaction, and NK1-agonist-induced foot tapping. Lesioned gerbils exhibited reduced immobility time during fear conditioning, a non-significant reduction in immobility time when re-exposed to the conditioned stimulus (CS) 24 h later, and increased social interaction in the gerbil social interaction task. In contrast, BLA lesions had no effect on NK1-agonist-induced foot tapping. These data provide further support that the gerbil BLA is a potential site for NK1 receptor antagonists to attenuate anxiety-related behaviours.