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Transfer of dopamine in the olfactory pathway following nasal administration in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2000 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 17, no 6, 737-742 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. The precise localisation of dopamine radioactivity in the brain was studied using autoradiography. The presence of dopamine or its metabolites in the olfactory bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS: After administration of [3H]-dopamine into the right nostril, the amount of dopamine in the right bulb increased with time until. after 4 h, it was 27 times higher than in the left bulb. Among the other brain tissue samples, significantly higher amount of radioactivity was detected in the lateral olfactory tract. Radioactivity in the right olfactory bulb was shown by autoradiography to be selectively located in the peripheral layers 1 to 4 h after administration. Selective uptake of radioactivity was not seen in other regions of the brain. TLC data indicated that approximately 75% and 10% of the radioactivity in the olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The results indicate that unchanged dopamine is transferred into the olfactory bulb following nasal administration of [3H]-dopamine.

Place, publisher, year, edition, pages
2000. Vol. 17, no 6, 737-742 p.
Keyword [en]
nasal administration, dopamine, mice, olfactory pathway, autoradiography
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91194DOI: 10.1023/A:1007542618378ISI: 000088665300017PubMedID: 10955850OAI: oai:DiVA.org:uu-91194DiVA: diva2:163846
Available from: 2004-01-07 Created: 2004-01-07 Last updated: 2011-03-08Bibliographically approved
In thesis
1. Models for the Transfer of Drugs from the Nasal Cavity to the Central Nervous System
Open this publication in new window or tab >>Models for the Transfer of Drugs from the Nasal Cavity to the Central Nervous System
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The blood-brain barrier restricts the access of many compounds, including therapeutic agents, to the brain. Several human studies indicate that nasal administration of hydrophilic compounds, such as peptides, can bypass the blood-brain barrier. The aims of this thesis were to develop and refine models for this direct nose-to-brain transfer.

In a mouse model, [3H]-dopamine was given as a unilateral nasal dose. The resulting radioactivity in the ipsilateral olfactory bulb was significantly higher than that in the contralateral bulb and peaked at 4 h. Tape section autoradiography showed that the radioactivity was concentrated in the olfactory nerve layer and the glomerular layer of the olfactory bulb. The olfactory transfer of dopamine was also studied in vitro. At a lower donor concentration, the mucosal-to-serosal dopamine permeability was higher than the serosal-to-mucosal permeability, but at a higher concentration, the permeability coefficients were similar. Together, these results suggest that the olfactory transfer of dopamine has an active component.

Olfactory transfer of fluorescein-labeled dextran through the epithelium and deeper tissues was studied in a rat model, which enabled visualization of the transfer using fluorescence microscopy. Although the epithelial transfer appeared to be mainly intracellular, transfer in the following deeper tissues was extracellular. Without altering the route of uptake, a gellan gum formulation enhanced the uptake of fluorescein dextran. The enhancing effect was considered likely to be the result of an increased residence time in the nasal cavity.

In conclusion, dopamine and fluorescein-labeled dextran were identified as suitable model compounds for the study of olfactory drug transfer mechanisms and the influence of drug formulation. Two new in vitro models of olfactory transfer were compared. Also, a rat model, which enabled the visualization of the entire nose-to-brain transfer, was developed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 46 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 305
Keyword
Biopharmacy, Administration, intranasal, Nasal mucosa, Central nervous system, Olfactory bulb, Rat, Mouse, Swine, Cattle, Diffusion chambers, culture, In vitro, Biological models, Biological transport, Dextrans, Dopamine, Gels, Polysaccharides, Autoradiography, Fluorescence microscopy, Biofarmaci
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-3905 (URN)91-554-5834-3 (ISBN)
Public defence
2004-01-30, B21, Uppsala biomedicinska centrum, Husargatan 3, Uppsala, 10:15
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Available from: 2004-01-07 Created: 2004-01-07Bibliographically approved

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