Comparison of the effects of selected drugs on the release of hypothalamic adrenaline and noradrenaline measured in vivo

Abstract

Intracerebral dialysis combined with high-performance liquid chromatography and electrochemical detection was used to monitor changes in extracellular posterior hypothalamic, noradrenaline, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) following administration of an inhibitor of phenylethanolamine-N-methyltransferase (LY87130); the alpha 2-antagonist idazoxan; the monoamine oxidase (MAO) inhibitor tranylcypromine, and a selective noradrenergic neurotoxin (DSP4) to the anaesthetised rat. LY87130 (50 mg/kg i.p.) decreased basal hypothalamic perfusate and whole-tissue levels of adrenaline by 100% and 64%, respectively, but was without effect on basal extracellular hypothalamic levels and whole-tissue levels of noradrenaline, DOPAC and 5-HIAA. Administration of the alpha 2-adrenoceptor antagonist idazoxan and the MAO inhibitor tranylcypromine elicited increases in hypothalamic extracellular levels of both adrenaline and noradrenaline by 208% and 229%, respectively. Idazoxan also increased hypothalamic extracellular 5-HIAA by 97% but was without effect on extracellular DOPAC. In contrast, tranylcypromine decreased hypothalamic extracellular levels of DOPAC and 5-HIAA by 72% and 50%, respectively. DSP4 depleted extracellular hypothalamic adrenaline and noradrenaline 360 min and 390 min postdrug, respectively, after causing an initial 3-fold increase in both these amines 150 min after drug administration. DSP4 was without effect on posterior hypothalamic extracellular DOPAC and 5-HIAA. These results demonstrate that the pharmacology of central adrenaline and noradrenaline is very similar and, with the exception of phenylethanolamine-N-methyl transferase inhibitors, none of the drugs investigated are able to differentiate between adrenergic and noradrenergic neurones.