ELECTRON-MICROSCOPIC LOCALIZATION OF TRITIATED NOREPINEPHRINE IN RAT BRAIN: EFFECT OF DRUGS

¹ Departments of Psychiatry and Anatomy, Yale University School of Medicine, and the Connecticut Mental Health Center, New Haven, Connecticut

The cellular localization of tritiated norepinephrine (H³-NE) injected into the cerebral ventricular system was studied by electron-microscopic autoradiography. The distribution of autoradiographic grains in control and drug-pretreated (reserpine and desmethylimipramine) animals was compared. In the controls, intraventricular injection of H³-NE resulted in intense autoradiographic activity over nerve endings and axons in the hypothalamus and caudate nucleus. Hypothalamic endings with autoradiographic activity also usually contained some dense-core (granular) vesicles. Reserpine (2 mg/kg i.v.) given 2 hr prior to the H³-NE almost completely abolished the autoradiographic activity. However, the dense-core vesicles were unchanged in number or electron density. Forty-eight hours after reserpine treatment there was considerable recovery of the ability of endings to retain the H³-NE and the pattern of localization of autoradiographic activity was almost identical to the controls. For example, in the hypothalamus, grains were again over endings with dense-core vesicles. Pretreatment with desmethylimipramine (20 mg/kg) also did not alter the normal cellular patterns of localization. These results suggest that certain nerve endings (e.g., in hypothalamus and caudate) can accumulate the H³-NE given via the ventricular route. The rapid return in the ability of nerve endings to retain H³-NE 48 hr after reserpine is correlated with gross behavioral recovery.

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