Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT1Areceptors
| Autor: | Joaquín Del Río, Ana Otano, Ana Garcia-Osta, Diana Frechilla, Santiago Ballaz |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pharmacology
Agonist medicine.medical_specialty Chemistry medicine.drug_class 8-OH-DPAT musculoskeletal neural and ocular physiology Hippocampus Ritanserin Partial agonist Buspirone chemistry.chemical_compound Endocrinology nervous system Internal medicine polycyclic compounds medicine heterocyclic compounds Serotonin Antagonists Receptor medicine.drug |
| Zdroj: | British Journal of Pharmacology. 128:1691-1698 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0702974 |
| Popis: | Pretraining administration of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT 0.1 mg kg−1), a 5-HT1A receptor agonist, or buspirone (1 mg kg−1), a 5-HT1A receptor partial agonist, markedly impaired passive avoidance retention in rats 24 h later. The effect of 8-OH-DPAT was prevented by the 5-HT1A receptor antagonists, NAN-190 and WAY-100635, at doses without any intrinsic effect. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ 10 mg kg−1), an alkylating agent that inactivates different G-protein coupled receptors, impaired retention performance when given 48 h pretraining. The disruptive effect of EEDQ was reversed by 8-OH-DPAT or buspirone, given 30 min before training. Non-specific actions did not account for 8-OH-DPAT-induced reversal of the EEDQ effect since no significant difference in locomotor activity or in pain threshold was found between rats receiving EEDQ or EEDQ+8-OH-DPAT. When NAN-190 (1 mg kg−1) or WAY-100635 (0.5 mg kg−1) were given before 8-OH-DPAT to EEDQ-pretreated animals, the reversal by 8-OH-DPAT of EEDQ-induced retention impairment was still more pronounced. However, no EEDQ reversal by 8-OH-DPAT was found when 5-HT1A receptors were protected by WAY-100635 (10 mg kg−1) 30 min before EEDQ. In the hippocampus of EEDQ-treated rats, 5-HT7 receptors were less inactivated than 5-HT1A receptors and significant increases were found in 5-HT1A but not in 5-HT7 receptor mRNA levels. Ritanserin and methiothepin (10 mg kg−1 each), antagonists with higher affinity at 5-HT7 than at 5-HT1A receptors, prevented the retention impairment induced by EEDQ but did not significantly protect against 5-HT7 receptor inactivation. The results indicate that the facilitatory effect of 8-OH-DPAT is not mediated through 5-HT1A receptors and suggest that other 8-OH-DPAT-sensitive receptors could be involved in the dual effect of 8-OH-DPAT on passive avoidance performance in rats. British Journal of Pharmacology (1999) 128, 1691–1698; doi:10.1038/sj.bjp.0702974 |
| Databáze: | OpenAIRE |
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