Norepinephrinergic reinnervation of cat occipital cortex following localized lesions with 6-hydroxydopamine

Abstract

We studied biochemical and morphological changes in central catecholamine (CA) terminals in the kitten visual cortex following direct infusion with 4 mM 6-hydroxydopamine (6-OHDA) for a week. Two zones may be distinguished within the cortical area affected by 6-OHDA (a radius of ∼ 10 mm). In the primary lesion zone (a radius of ∼ 5 mm) near the center of the 6-OHDA infusion, excluding an area of non-specific damage left by cannulation (a radius of < 1.5 mm), we found: (1) absence of fluorescent CA terminals by histochemistry; (2) very low desipramine-sensitive uptake of tritiated norepinephrine (NE) by cortical slices (desipramine-resistant NE uptake stayed high); (3) a 50% increase in β-adrenoreceptor binding sites by densitometry of light microscopic autoradiograms; and (4) low levels (< 20% of control) of endogenous NE and low to moderate levels (10–70%) of endogenous dopamine (DA). In the surrounding zone (about 5–10 mm from the infusion center), however, none of the above changes were observed, except for a moderate to substantial reduction (50–80% of control) in endogenous NE and a small (10–20%) reduction in endogenous DA. Within two weeks after the end of the cortical 6-OHDA infusion, the dimensions of the cortical area devoid of CA terminals became substantially smaller than those found earlier. Fluorescent CA terminals were seen virtually everywhere in the cortex by 4 weeks, including the scar left by placement of the infusion cannula. In 24 weeks CA terminals in the occipital cortex appeared close to normal in density as well as in fluorescence intensity. Biochemical assays also revealed the recovery trend of CA contents. A steady increase in the NE content was obtained in the surrounding zone, with the stronger trend at its periphery, eventually attaining full recovery in 23 weeks. The recovery was slow in the primary lesion zone, especially near the infusion center, though there was a continual increase in endogenous DA toward control even at the infusion center.