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Impairment of active avoidance by the noradrenergic neurotoxin, DSP4: attenuation by post-training epinephrine

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Male Sprague-Dawley rats were treated with the selective noradrenergic neurotoxin, DSP4 prior to behavioral assessment. They were trained in an inhibitory avoidance and a one-way active avoidance task and given post-training treatment with epinephrine (EPI, 0.1 mg/kg, SC) or physiological saline. Performance on these tests was assessed at time points after treatment with DSP4 when (1) both central NE and sympathetic catecholamines were depleted and when (2) sympathetic catecholamines had returned to control levels and central NE remained depleted. Activity was also assessed at two time points after DSP4 treatment. DSP4 treatment had no effect upon inhibitory avoidance retention but impaired one-way active avoidance shuttle performance at both time points following DSP4 treatment. There was a transient depression of spontaneous activity which may indicate a deficit of behavioral initiation during the early phase after DSP4 treatment when the sympathetic catecholamine levels were depleted. This finding suggests that the peripheral sympathetic system may support some aspect of behavioral initiation. Epinephrine (0.1 mg/kg SC) administered after active avoidance training ameliorated the active avoidance retention performance deficit seen 4 days after DSP4 treatment. Post-training EPI did not significantly affect active avoidance retention performance when animals were trained and tested after peripheral sympathetic recovery (approximately 2 weeks after DSP4 treatment). These findings suggest that peripheral adrenergic activation plays a role in the EPI facilitation of retention performance in this task. As the facilitatory effects of peripherally circulating epinephrine were expressed in the presence of a severely depleted dorsal noradrenergic bundle system, they do not appear to depend upon the stimulation of NE released from this system. The present data, however, do not exclude the possibility that the modulation by peripheral EPI may depend upon its stimulation of NE release at other loci of central noradrenergic innervation.

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Correspondence to James L. McGaugh.

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Bennett, M.C., Kaleta-Michaels, S., Arnold, M. et al. Impairment of active avoidance by the noradrenergic neurotoxin, DSP4: attenuation by post-training epinephrine. Psychopharmacology 101, 505–510 (1990). https://doi.org/10.1007/BF02244229

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Key words

  • DSP4
  • Dorsal noradrenergic bundle (DNB)
  • Norepinephrine
  • Epinephrine
  • Learning
  • Memory rats
  • Active avoidance