Two applications of in vivo brain microdialysis: administration of high-molecular-weight drugs through a microinjection tube and measurement of nitric oxide production

Abstract

A brain microdialysis technique has made it possible to determine neurotransmitter levels in the targeted region of the brain of a freely moving rat. In this article, two kinds of application of the brain microdialysis are demonstrated. First, to study central nervous effects of large molecular weight substances that cannot cross the blood-brain barrier, we used a microdialysis probe equipped with a microinjection tube for administering the substance in the same region into which the probe had been inserted. We proved that interleukin-1β (1 ng) injected directly into the anterior hypothalamus elicited releases of NE, DA and 5-HT, as well as increases in their metabolites. Second, using a new method combining a brain microdialysis technique with measurement of nitrite/nitrate by the Griess reaction, we demonstrated that activation of N-methyl-D-aspartate (NMDA) receptors in the cerebella of rats induces the release of nitric oxide (NO). Since L-N^G-monomethyl-arginine (L-NMMA), which competitively blocks NO synthesis from L-arginine, significantly inhibited the release of nitrite/nitrate from the rat cerebellum, these results indicate that this new method is capable of measuring NO formation from L-arginine following the stimulation of NMDA receptors.