Investigating the effect of bilateral amygdala lesions on fear conditioning and social interaction in the male Mongolian gerbil.
Identification of the selective neurokinin NK(1) 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 NK(1) 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 NK(1) receptor antagonists. The high levels of NK(1) receptor binding in the amygdala as well as preclinical studies demonstrating increased release of substance P and corresponding internalisation of NK(1) receptors in the basolateral amygdala in response to stressful stimuli suggest that the BLA may represent a potential site of action for NK(1) 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 NK(1)-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 NK(1)-agonist-induced foot tapping. These data provide further support that the gerbil BLA is a potential site for NK(1) receptor antagonists to attenuate anxiety-related behaviours.
Woolley
M L
ML
Pharma Research Neuroscience, F. Hoffmann-La Roche, CH-4070 Basel, Switzerland. marie.2.woolley-roberts@gsk.com
Haman
M
M
Higgins
G A
GA
Ballard
T M
TM
D000679:Amygdala / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000077608:Aprepitant; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005239:Fear / Q000502:physiology*; D005849:Gerbillinae; D007051:Ibotenic Acid / Q000633:toxicity; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D007398:Interpersonal Relations; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; C068032:GR 73632; D000077608:Aprepitant; D007051:Ibotenic Acid; D013373:Substance P