Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents.
The aim of this study was to investigate whether morphine can be transferred along the olfactory pathway to the CNS, thereby circumventing the blood-brain barrier, after nasal administration to rodents. Radiolabelled and unlabelled morphine were administered via the right nostril to mice and rats. Olfactory bulbs, brain tissue and blood samples were collected. Morphine-derived radioactivity was measured using liquid scintillation (LS) and the concentrations of morphine and its metabolite morphine-3-glucuronide (M3G) were also assessed with high-performance liquid chromatography. The location of morphine-derived radioactivity in the rat brain was visualised by autoradiography. Overall, the levels of morphine in the right olfactory bulbs (ROBs) significantly exceeded those in the left olfactory bulbs (LOBs) and brain tissue samples 15, 60 and 240 min after right-sided nasal administration. Fifteen minutes after intravenous administration, there were no significant differences between olfactory bulbs and the other brain areas. Five minutes after nasal administration, autoradiography revealed radioactivity surrounding the ROB and reaching one of the ventricles in the brain. After 60 min, radioactivity had reached the peripheral parts of the ROB. All the techniques used in this study demonstrate that morphine was transferred along the olfactory pathway to the CNS after nasal administration to rodents.
Westin
Ulrika
U
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden.
Piras
Elena
E
Jansson
Björn
B
Bergström
Ulrika
U
Dahlin
Maria
M
Brittebo
Eva
E
Björk
Erik
E
D000281:Administration, Intranasal; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009833:Olfactory Pathways / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D014316:Tritium; D009020:Morphine