Dose-response relationship for nicotine-induced up-regulation of rat brain nicotinic receptors
| Autor: | Maureen Li, Peter P. Rowell |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Nicotine Central nervous system Pharmacology Receptors Nicotinic Biochemistry Drug Administration Schedule Injections Rats Sprague-Dawley Cellular and Molecular Neuroscience Cytisine chemistry.chemical_compound Desensitization (telecommunications) In vivo Internal medicine medicine Animals Tissue Distribution Receptor Infusion Pumps Acetylcholine receptor Dose-Response Relationship Drug Chemistry Brain Rats Up-Regulation Nicotinic acetylcholine receptor Endocrinology medicine.anatomical_structure medicine.drug |
| Zdroj: | Journal of neurochemistry. 68(5) |
| ISSN: | 0022-3042 |
| Popis: | The chronic administration of nicotine to animals has been shown to result in an increase in brain nicotinic acetylcholine receptor (nAChR) density. It has been suggested that this agonist-induced receptor up-regulation is a consequence of long-term nAChR desensitization in vivo. In this study, the effects of different nicotine doses and administration schedules as well as the resulting blood and brain nicotine levels were determined to assess the effect of in vivo nicotine concentration on nAChR density in the brain. Rats with indwelling subcutaneous cannulas were infused for 10 days with 0.6–4.8 mg/kg/day nicotine either 2×, 4×, or 8×/day or by constant infusion. The nAChR density in cortical, striatal, and hippocampal tissue measured by [3H]cytisine binding as well as the corresponding plasma and brain nicotine levels measured by GC analysis were determined. The results showed a dose-dependent increase in nAChR density with significant increases achieved at 2.4 mg/kg/day in all three brain areas. It is surprising that at this dose there was little difference between the constant infusion of nicotine and twice-daily administration, whereas more frequent periodic injections were actually less effective at up-regulating nAChRs. An analysis of the blood and brain levels of nicotine compared with the concentrations that produce nAChR desensitization suggests that in vivo desensitization alone is not sufficient for nAChR up-regulation to occur. |
| Databáze: | OpenAIRE |
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