Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration

Nicole Ducharme, William A. Banks, John E. Morley, Sandra M. Robinson, Michael L. Niehoff, Claudia Mattern

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake. Bioavailability based on appearance in arterial serum showed that about 23% and 14% of the intranasal administered doses of pregnenolone and progesterone, respectively, entered the blood. Brain levels were about two fold lower after intranasal administration for the two neurosteroids. With intranasal administration, brain levels of the two steroids did not vary over time (2-120. min), whereas brain levels were higher early (10. min or less) after i.v. administration. With i.v. administration, uptake by brain regions did not vary, whereas the olfactory bulb, hippocampus, and hypothalamus had high uptake rates after intranasal administration. Intranasal administration of prenenolone improved memory, whereas progesterone decreased anxiety, thus demonstrating that therapeutic levels of neurosteroids can be delivered to the brain by intranasal administration. The neurosteroids were rapidly degraded after i.v. or intranasal delivery, but pregnenolone was more resistant to degradation in the brain after intranasal administration and in serum after i.v. administration. These results show that either the i.v. or intranasal routes of administration can deliver neurosteroids to blood and brain, but that the two routes have significant differences with intranasal administration favoring some brain regions.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Sep 2010


  • Anxiety
  • Intranasal
  • Memory
  • Neurosteroid
  • Pregnenolone
  • Progesterone


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