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[³H]Methotrexate Loss from the Rat Brain following Enhanced Uptake by Osmotic Opening of the Blood-Brain Barrier

Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, Maryland 20205 [M. O., W. R. F., U. S., S. I. R.], and Department of Neurosurgery, School of Medicine, Oregon Health Sciences University, Portland, Oregon 96201 [E. A. N.]

Right brain regions of anesthetized rats were loaded with [3,5,7-³H]methotrexate ([³H]MTX) or with [¹⁴C]sucrose by infusing the tracers into the right carotid artery, after the blood-brain barrier had been opened by right carotid infusion of a hypertonic arabinose solution. During the 6 hr following the procedure, the [³H]MTX concentration in 7 right-sided brain regions, when normalized to the plasma concentration integral during tracer infusion, fell, with an average half-time of 4.8 hr as compared to less than 20 min for the initial rate of loss of [¹⁴C]sucrose. Right-left brain concentration differences 3 hr after treatment were statistically significant (p < 0.05) for [³H]MTX but not for [¹⁴C]sucrose. The results indicate that intracerebral [³H]MTX is lost more slowly than is intracerebral [¹⁴C]sucrose, possibly because [³H]MTX enters brain cells, whereas [¹⁴C]sucrose remains largely extracellular.

¹ Supported in part by NIH Grant CA 27191 and the Veterans Administration.

² To whom requests for reprints should be addressed.

Received 1/19/81. Accepted 11/ 6/84.