Denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 [N (2-chloroethyl)-N-ethyl-2-bromobenzylamine] reduces dopamine release potential in the nucleus accumbens shell in conscious rats.

Pretreatment with DSP-4, a neurotoxin highly selective for the locus coeruleus (LC) noradrenergic projections, 2 weeks before in vivo microdialysis in conscious rats had no effect on baseline extracellular dopamine (DA) levels in the nucleus accumbens shell, but reduced dose-dependently the dopamine response to depolarisation induced by 50 mM KCl. DA metabolism in the frontal cortex, as measured ex vivo, was increased in animals treated with a low (10 mg/kg) but not with a high dose (50 mg/kg) of DSP-4, possibly indicating an increased sensitivity to stress in these animals and thus suggesting differential regulation of DA in the forebrain by the LC lesions. The reduced DA release potential in the nucleus accumbens after DSP-4 treatment suggests that weakening of the LC input to DA nerve cells contributes to motivational deficits.