Further characterization of brain 3,4-dihydroxyphenylethyleneglycol (DHPG) formation: dependence on noradrenergic activity and site of formation

Abstract

The dependence of brain and plasma 3,4-dihydroxyphenylethyleneglycol (DHPG) formation upon CNS noradrenergic neutronal activity was evaluated following manipulations that are known to alter the firing rate of the locus coeruleus (LC) neurons and as a consequence, noradrenaline (NA) release and turnover. In addition, the relative degree of intraneuronal formation of brain DHPG was assessed by studying the metabolism of released NA during uptake inhibition. Electrical stimulation of the LC for 20 min induced an increase in rat cortical (40-42%), hypothalamic (22-29%) and plasma (68-79%) total DHPG and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels. Two hours following administration of the alpha-2 adrenoceptor antagonist yohimbine (10 mg/kg, i.p.), rat brain cortical conjugated DHPG and MHPG as well as free MHPG concentrations were increased whereas cortical free DHPG levels remained unchanged. The same treatment also increased plasma total DHPG and MHPG levels. In mice given the NA uptake inhibitor desipramine (10 mg/kg, i.p.) 2 h prior to sacrifice, brain free DHPG and MHPG concentrations were significantly reduced by 30 and 40%, respectively, whereas yohimbine (1-20 mg/kg, i.p.) induced a dose-dependent increase in brain DHPG (60-80%) and MHPG (60-220%) concentrations. Pretreatment with desipramine (10 mg/kg, i.p.) 30 min prior to yohimbine reduced, in rat, or abolished, in mice, the yohimbine-induced elevation of brain DHPG levels. In contrast, desipramine augmented the effect of yohimbine on brain MHPG levels resulting in a shift to the left of the dose response curves. These findings indicate that brain and plasma DHPG levels are sensitive to changes in brain noradrenergic neuronal impulse flow.(ABSTRACT TRUNCATED AT 250 WORDS)