Electrophysiological and biochemical sequelae of the destruction of hippocampal noradrenergic afferents by DSP4.

The effects of DSP4 lesions were examined 20-53 days postlesion in the rat hippocampus. A single treatment with DSP4 produced decreases of 42-94% in the norepinephrine (NE) content of this brain region. There was, however, no effect of DSP4 treatment on either the number or affinity of beta-adrenergic receptor sites as determined by radioligand binding studies with (-)-[125I]pindolol; furthermore, there was no relationship between the concentrations of NE and the number of receptor sites in individual hippocampi. The DSP4-induced depletion of functionally releasable NE was confirmed by the loss of electrophysiological responsiveness to amphetamine in the in vitro hippocampus following such lesions. In contrast, electrophysiological responses to direct acting beta-adrenergic or alpha-adrenergic agonists were unchanged following DSP4 treatment. This finding again suggests the lack of any change in postsynaptic sensitivity. The results of this study demonstrate that while the potent noradrenergic neurotoxin DSP4 is able to reduce NE concentrations significantly in noradrenergic target regions in brain, these lesions are not necessarily associated with postsynaptic changes in adrenergic systems.