DSP-4 treatment produces abnormal tyrosine hydroxylase immunoreactive fibers in rat hippocampus

DSP-4 has been used as selective toxin for central norepinephrine (NE) systems. The depletion of NE by DSP-4 is though to result from neurotoxic destruction of locus coeruleus terminals and axons. We have used tyrosine hydroxylase immunocytochemistry (TH-IR), silver stains for neural degeneration, and electron microscopy to examine the morphological effects of DSP-4 treatment on the rat hippocampus. Animals survived for either 2 or 5 weeks after DSP-4 treatment. DSP-4 depleted hippocampal norepinephrine levels to 15% of control values. Abnormally enlarged TH-IR fibers were found in the hippocampus of DSP-4-treated animals. No evidence of fiber degeneration was found following light or electron microscopic examination of the dentate hilus in DSP-4-treated animals. These data suggest that DSP-4 treatment does not destroy NE terminals, but may produce an intraneuronal lesion leading to an accumulation of TH and a depletion of norepinephrine within the terminal fields.