An improved pharmacological procedure for depletion of noradrenaline: pharmacology and assessment of noradrenaline-associated behaviors☆

Abstract A pharmacological procedure which initially depletes noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) but permits repletion of DA and 5-HT was used to evaluate the role of NA in feeding behavior and intracranial self-stimulation behavior. The rapid-onset ‘reserpine-like’ vesicular depletion drug RO 4-1284 reduced NA and 5-HT 99% and DA 90% in rat forebrain within 1 h after administration with complete repletion of all amines occurring within 6 to 12 h. Treatment with the dopamine-β-hydroxylase inhibitor FLA-63 significantly reduced NA (maximum depletion 42%) but not DA or 5-HT over the 12 h period of evaluation. The two drugs together produced a specific depletion of NA. Forebrain levels of NA in subjects pretreated with FLA-63 then given RO 4-1284 0.5 h later were reduced to 2% of control values for 8 h while vesicular stores of DA and 5-HT were repleted 77% and 93%, respectively, within 8 h after administration. Selective depletion of NA, in this manner, reduced deprivation induced food intake and lateral hypothalamic self-stimulation.