A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat

Abstract

1 The effects of various doses of DSP4 on two-way active avoidance acquisition in rats and on central noradrenaline neurones were compared. 2 Doses of DSP4 from 3 mg kg⁻¹ i.p. and upwards injected one week before the onset of the avoidance trials significantly impaired two-way avoidance learning. 3 The learning impairment caused by DSP4 (50 mg kg⁻¹ i.p.) lasted for at least 10 weeks. 4 Desipramine (20 mg kg⁻¹) injected either 30 or 60 min before DSP4 (50 mg kg⁻¹) antagonized the active avoidance impairment. 5 A high dose of DSP4 (50 mg kg⁻¹ i.p.) produced profound decreases in dopamine-β-hydroxylase activity in the frontal cortex and in the concentrations of noradrenaline in various brain regions indicating degeneration of the locus coeruleus noradrenaline system. 6 Low doses of DSP4 (3 and 6 mg kg⁻¹ i.p.) produced small but significant decreases in the concentrations of noradrenaline (NA) in some regions, e.g. cerebral cortex, hippocampus, olfactory bulb and spinal cord. 7 The avoidance impairment caused by the low dose of DSP4 (3 mg kg⁻¹) was absent when rats were tested 10 weeks after treatment nor was NA depletion present when NA was analysed 3 months after treatment.