Effects of yohimbine and idazoxan on monoamine metabolites in rat cerebrospinal fluid

Abstract

Effects of two alpha 2-adrenoceptor antagonists, idazoxan and yohimbine, on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were investigated. Both drugs caused a dose-dependent, up to 250% increase in the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) in CSF indicating enhanced release, metabolism and turnover of noradrenaline in the central nervous system (CNS). In addition, a similar increase in homovanillic acid (HVA) in CSF was observed, while the level of 5-hydroxyindoleacetic acid was unchanged. The present results demonstrate the usefulness of monitoring drug-induced alterations in noradrenergic activity in the CNS by measurement of free MHPG in repeatedly collected cisternal CSF samples from awake rats. The possibility that the observed increase in the concentration of HVA after the highly specific alpha 2-antagonist idazoxan reflects increased noradrenergic rather than dopaminergic neuronal activity is discussed.