EVIDENCE THAT THE AMYGDALA IS INVOLVED IN THE DISINHIBITORY EFFECTS OF 5-HT3-RECEPTOR ANTAGONISTS

The effects of various 5-HT3 receptor antagonists were examined in the social interaction (SI) test following discrete microinjection into either the dorsal raphe nucleus (DRN) or amygdala of the rat. Following DRN injection, ondansetron, ICS205-930, and MDL72222 (5-500 ng) all failed to modify SI under high light/unfamiliar (HLU) test conditions relative to vehicle pretreated controls. The 5-HT, receptor agonist, 2-Me 5-HT (100-2500 ng), was similarly ineffective under both HLU and low light/familiar (LLF) conditions, although 5-HT (20-100 ng) increased SI under the HLU paradigm. After amygdaloid injection, ondansetron (10-100 ng), granisetron (1-10 ng), ICS205-930 (10-100 ng), GR 65630 (1-10 ng), and MDL72222 (100-1000 ng) all significantly increased SI under the HLU but not LLF condition. Furthermore, a detailed behavioural analysis revealed that the behaviours underlying this increase were similar to those seen in vehicle pretreated animals tested in the LLF compared to HLU condition. The benzodiazepine, flurazepam (200 ng), increased both SI (HLU condition) and punished responding in a modified water-lick conflict model, after amygdaloid injection. Both ondansetron (10-1000 ng) and ICS205-930 (1-100 ng) were ineffective in the conflict test. Finally, 2-Me 5-HT and 5-HT (100-10 000 ng) reduced SI under the LLF test condition with no concomitant change in locomotor activity. It is concluded that the amygdala, but not the DRN, may represent an important neuroanatomical locus for the disinhibitory, perhaps anxiolytic, properties of 5-HT3 receptor antagonists.