Lesions of NE Neurons

Lesions of NE neurons can be achieved by different methods, including excitotoxic lesion of the locus ceruleus, local administration of 6-hydroxydopamine in the main LC projection pathway, or systemic administration of DSP-4. Although easy to use because of the possibility of a systemic injection, DSP-4 is not a suitable tool because it only induces a 70% loss in tissue NE and makes interpretations difficult when no behavioral deficit is observed.

In the rat, nearly complete depletion of NE (> 99%) in the forebrain can be achieved by injecting 6-hydroxydopamine, a neurotoxin selective of the catecholaminergic neurons locally into the trajectory of the LC axons, i.e., the dorsal noradrenergic bundle (DNAB). Such a lesion has no effect on eating, drinking, or spontaneous locomotor behavior but affects responses to novelty and the acquisition of conditioned behavior. DNAB lesions impair appetitive and aversive conditioning whenever the rat has to learn a behavior in response to the discriminative stimulus, but only when the lesion occurred before the acquisition of the task. Tasks in which a simple behavioral response is required, such as conditioned taste aversion, are resistant to DNAB lesion. DNAB lesion also spares behavioral tasks in which the animal has to refer to distal cues, as in contextual aversive conditioning or spatial learning in a Morris maze. Taken together, these results suggest that DNAB-lesioned animals are only impaired in tasks requiring a high level of arousal and focused attention to local cues. Additionally, DNAB lesions have been shown to exert anxiolytic effects in anxiogenic behavioral test situations.

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