Preclinical profile of the mixed 5-HT1A/5-HT2A receptor antagonist S 21357
| Autor: | Marie-Claire Rettori, B Guardiola-Lemaı̂tre, D. Caroline Blanchard, Robert J. Blanchard, Guy Griebel |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Clinical Biochemistry In Vitro Techniques Motor Activity Pharmacology Toxicology Synaptic Transmission Biochemistry Rats Sprague-Dawley Mice Behavioral Neuroscience Dorsal raphe nucleus Piperidines Internal medicine Avoidance Learning medicine Animals Benzothiazoles Biological Psychiatry 5-HT receptor Brain Chemistry Behavior Animal Dose-Response Relationship Drug 5-HT2 receptor Antagonist Lesopitron Receptor antagonist Rats Electrophysiology Thiazoles Endocrinology Anti-Anxiety Agents Receptors Serotonin Raphe Nuclei 5-HT1A receptor Serotonin Antagonists Serotonin Psychology Adenylyl Cyclases |
| Zdroj: | Pharmacology Biochemistry and Behavior. 54:509-516 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/0091-3057(95)02215-5 |
| Popis: | This study evaluated the pharmacological and behavioral effects of S 21,357, a drug with high affinity for both 5-HT1A and 5-HT2A receptors. The drug behaved as antagonist at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors, as it prevented the inhibitory effect of lesopitron on the electrical discharge of the dorsal raphé nucleus (DRN) 5-HT neurons and the activity of forskolin-stimulated adenylate cyclase in hippocampal homogenates. In addition, S 21,357 (4 and 128 mg/kg, PO) inhibited 5-HTP-induced head-twitch responses in mice, indicating that it possesses 5-HT2A antagonistic properties. In a test battery designed to assess defensive behaviors of Swiss-Webster mice to the presence of, or situations associated with, a natural threat stimulus (i.e., rat), S 21,357 (0.12-2 mg/kg, IP) reduced contextual defense reactions after the rat was removed, risk assessment activities when the subject was chased, and finally, defensive attack behavior. These behavioral changes are consistent with fear/anxiety reduction. Furthermore, the drug strongly reduced flight reactions in response to the approaching rat. This last finding, taken together with recent results with panic-modulating drugs, suggest that S 21,357 may have potential efficacy against panic attack. Finally, our results suggest that compounds sharing high affinities for both 5-HT1A and 5-HT2A receptors may directly or synergistically increase the range of defensive behaviors affected. |
| Databáze: | OpenAIRE |
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