Evidence that the amygdala is involved in the disinhibitory effects of 5-HT 3 receptor antagonists

Evidence that the amygdala is involved in the disinhibitory effects of 5-HT 3 receptor antagonists 213 104 104 4 4 Guy A. Higgins Brian J. Jones Nigel R. Oakley Michael B. Tyers Department of Neuropharmacology Glaxo Group Research Ltd. SG12 0DP Ware Herts UK Addiction Research Foundation 33 Russell Street M5S 2S1 Toronto Ontario Canada Smith Kline Beecham Pharmaceuticals Coldharbour Road, The Pinnacles CM19 5AD Harlow Essex UK Abstract The effects of various 5-HT 3 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 3 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-HT 3 receptor antagonists. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Evidence that the amygdala is involved in the disinhibitory effects of 5-HT 3 receptor antagonists

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Publisher
Springer Journals
Copyright
Copyright © 1991 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/BF02245664
Publisher site
See Article on Publisher Site

Abstract

213 104 104 4 4 Guy A. Higgins Brian J. Jones Nigel R. Oakley Michael B. Tyers Department of Neuropharmacology Glaxo Group Research Ltd. SG12 0DP Ware Herts UK Addiction Research Foundation 33 Russell Street M5S 2S1 Toronto Ontario Canada Smith Kline Beecham Pharmaceuticals Coldharbour Road, The Pinnacles CM19 5AD Harlow Essex UK Abstract The effects of various 5-HT 3 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 3 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-HT 3 receptor antagonists.

Journal

PsychopharmacologySpringer Journals

Published: Aug 1, 1991

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