Blockade of cocaine sensitization and tolerance by the co-administration of odansetron, a 5-HT 3 receptor antagonist, and cocaine
| Autor: | G. R. King, Everett H. Ellinwood, Z. Xiong |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Narcotics Injections Subcutaneous Narcotic Antagonists medicine.medical_treatment Pharmacology 5-HT3 receptor Rats Sprague-Dawley Ondansetron 5-HT3 Receptor Antagonist Cocaine Drug tolerance medicine Animals Saline Sensitization Drug Implants Behavior Animal Dose-Response Relationship Drug biology business.industry Antagonist Drug Tolerance Rats Substance Withdrawal Syndrome medicine.anatomical_structure Anesthesia Toxicity biology.protein Serotonin Antagonists business medicine.drug |
| Zdroj: | Psychopharmacology. 130:159-165 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s002130050224 |
| Popis: | The present experiment evaluated the ability of the 5-HT3 antagonist, ondansetron, administered during chronic cocaine administration, to block the development of sensitization and tolerance induced by the intermittent or continuous administration of cocaine, respectively. Rats were pretreated with 40 mg/kg per day cocaine for 14 days by either SC injections or osmotic minipumps, or 0.9% saline, administered by SC injection. During this chronic (cocaine) treatment, all rats received a daily SC injection of 0-1.0 mg/kg ondansetron. The rats were then withdrawn from the pretreatment regimen for 7 days. On day 7 of withdrawal from the cocaine pretreatment all subjects received a 15.0 mg/kg IP cocaine challenge, and their behavior was then rated according to the modified Ellinwood and Balster scale for 60 min. The results indicated that daily injections of ondansetron had no consistent or significant effect on the subsequent behavioral response to cocaine in the saline control subjects. In contrast, daily injections of ondansetron with cocaine significantly blocked the development of sensitization with an inverted U-shape dose-response curve. In the continuous cocaine group ondansetron injections also attenuated the development of behavioral tolerance. The results therefore indicate that 5-HT3 receptor stimulation during continuous and intermittent cocaine administration is an important link in the development of behavioral tolerance and sensitization. |
| Databáze: | OpenAIRE |
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