The effects of continuous 5-HT3 receptor antagonist administration on the subsequent behavioral response to cocaine
| Autor: | Jennifer Konen, Sophie Tran, George R King, Gail Pinto, Craig R. Hilburn, Gene Castro |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Indazoles Indoles Tropisetron Central nervous system Down-Regulation Motor Activity Pharmacology Rats Sprague-Dawley 5-HT3 Receptor Antagonist Cocaine Internal medicine medicine Animals Receptor Infusion Pumps 5-HT receptor Sensitization Behavior Animal Dose-Response Relationship Drug business.industry Rats Substance Withdrawal Syndrome Blockade medicine.anatomical_structure Endocrinology Receptors Serotonin Serotonin Antagonists Receptors Serotonin 5-HT3 Stereotyped Behavior business Reverse tolerance Tropanes medicine.drug |
| Zdroj: | European Journal of Pharmacology. 449:253-259 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(02)02036-8 |
| Popis: | A functional down-regulation of central serotonin3 (5-HT3) receptors represents a partial mechanism of the tolerance to cocaine induced by the continuous administration of cocaine. Blocking this down-regulation by co-administering continuous cocaine and daily injections of 5-HT3 receptor antagonists blocks the development of tolerance. The present experiment evaluated the ability of continuously administered 5-HT3 receptor antagonists, to induce sensitization (reverse tolerance) to the behavioral effects of cocaine, based on the hypothesis that chronic blockade of 5-HT3 receptors should induce an up-regulation of these receptors. In all experiments, rats received a 14 day pretreatment involving the continuous administration of tropisetron (0.0, 1.0, 4.0, or 8.0 mg/kg/day) or LY 278,584 (0.001, 0.01, or 0.1 mg/kg/day). The rats were withdrawn for 7 days from this pretreatment regimen. On day 7 of withdrawal from the pretreatment regiment, the rats received a 0.0, 7.5, or 15.0 mg/kg i.p. cocaine challenge. Ambulatory behavior was automatically recorded for 60 min. Both continuous tropisetron and LY 278,584, opposite to the initial hypothesis, induced tolerance, and not sensitization, to the behavioral effects of cocaine. The results clearly indicate that central 5-HT3 receptors are critical for the effects of chronic cocaine administration. |
| Databáze: | OpenAIRE |
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