Hypothalamic microinjection of norepinephrine (NE) elevates and prolongs basal efflux of unmetabolized NE from injection site.

The effect of a microinjection of norepinephrine (NE) into the diencephalon of the rat was examined in terms of the subsequent endogenous activity of this amine. A push-pull guide cannula was first implanted stereotaxically with the tip resting in the rat's hypothalamus. Several days later, NE in a dose of 20 ng, 95 ng or 3.2 micrograms was microinjected in a volume of 0.5 microliters into the perifornical region. After a 30 min interval, the injection site was perfused, by means of push-pull cannulae with an artificial CSF at a rate of 25 microliters/min. The samples of perfusate collected one hour after the microinjection were analyzed by HPLC with electrochemical detection. The results indicate that an unexpectedly high level of unmetabolized NE can be detected at the perfusion site. This NE is greater than the picogram quantities of NE present endogenously in the rat's hypothalamus. The persistent presence of the exogenously applied amine within a microinjection site could explain the longevity of a given pharmacological effect of an amine often seen with this injection procedure. Also, it suggests that the local metabolic degradation of the amine is not as rapid as one would expect.