Lesioning of Locus coeruleus projections by DSP-4 neurotoxin treatment: Effect on amphetamine-induced hyperlocomotion and dopamine D-2 receptor binding in rats

DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminal s of the locus coeruleus projections. Data on the effect of DSP-4 treatment on amphetamine-induced hyperlocomotion are contradictory. In this study, D SP4 (50 mg/kg) caused reduction of noradrenaline levels by 70% in the cereb ral cortex and by 79% in the cerebellum. This treatment resulted in upregul ation of dopamine D-2 receptors in the striatum as evidenced by [H-3]-raclo pride binding. In an open field test, DSP-4 reduced locomotor activity. D-A mphetamine (1.5 mg/kg) caused a similar increase in locomotor activity in c ontrol and DSP-4-pretreated animals not familiar to the apparatus. However, when the rats were habituated to the test apparatus, the effect of ampheta mine on horizontal activity was significantly larger in the DSP-4-pretreate d animals. These data suggest that supersensitivity of Da receptors develop s after locus coeruleus denervation, but that the enhanced efficacy of amph etamine in DSP-4-treated rats is masked by neophobia.