Serotonin 5-HT1a receptor-mediated hypothermia in mice: Absence of spare receptors and rapid induction of tolerance
| Autor: | Emanuel Meller, Karen Bohmaker, Michael Chalfin |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty medicine.drug_class Clinical Biochemistry Hypothermia Toxicology Biochemistry Piperazines Body Temperature Mice Behavioral Neuroscience chemistry.chemical_compound Internal medicine polycyclic compounds medicine Animals Pindolol Receptor Adrenergic alpha-Antagonists Biological Psychiatry 5-HT receptor Pharmacology 8-Hydroxy-2-(di-n-propylamino)tetralin 8-OH-DPAT musculoskeletal neural and ocular physiology Colforsin Fenclonine Drug Tolerance Endocrinology nervous system chemistry Receptors Serotonin Quinolines 5-HT1A receptor medicine.symptom medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 43:405-411 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/0091-3057(92)90169-g |
| Popis: | The mixed 5-hydroxytryptamine1A (5-HT1A) receptor agonist/antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol-[4.5]-decane-7,9-dione (BMY 7378) (5 mg/kg) did not significantly depress body temperature, but pretreatment with BMY 7378 blocked hypothermia induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In contrast, another partial 5-HT1A agonist, pindolol (10 mg/kg), slightly but significantly depressed body temperature by itself but did not attenuate hypothermia elicited by 8-OH-DPAT. Attempts to identify the synaptic locus of the receptor were unsuccessful because depletion of central serotonin (5-HT) by treatment with para-chlorophenylalanine (PCPA; 3 × 150 mg/kg) did not alter the hypothermic response to 8-OH-DPAT. Partial, irreversible 5-HT1A receptor inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (1 mg/kg) reduced the maximal hypothermic effect of 8-OH-DPAT (to 53% of control) without altering its ED50 (0.96 mg/kg). Analysis of the data indicated a linear relationship between 5-HT1A receptor occupancy and hypothermic response, that is, absence ofreceptor reserve. When groups of mice were treated with each of five different doses of 8-OH-DPAT (0.04, 0.16, 0.63, 2.5, and 10 mg/kg) 48 h apart, there was a significant reduction in hypothermic response after the second injection, but only at the three highest doses. The results demonstrate that 8-OH-DPAT-induced hypothermia in mice is mediated by a 5-HT1A receptor whose synaptic localization is uncertain but that has no receptor reserve. In addition, tolerance is observed after only a single agonist treatment. |
| Databáze: | OpenAIRE |
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