Electrically evoked noradrenaline release in the rat hypothalamic paraventricular nucleus studied by in vivo electrochemistry: Autoregulation by alpha-2 receptors

Abstract

Evoked noradrenaline release was monitored every 1 s in vivo from the hypothalamic para ventricular nucleus by differential pulse amperometry at + 105 mV combined with carbon fiber electrodes. Noradrenaline release was evoked by electrical stimulations of the ventrolateral medulla for 20 s every 10 min at a physiological frequency (3–20 Hz) (see accompanying paper). The evoked noradrenaline release was dose-dependently attenuated by clonidine (10–100 μg/kg, i.v.) and strongly enhanced by alpha-2 antagonists: yohimbine (2 mg/kg), piperoxane (2 mg/kg) and idazoxan (0.05–1 mg/kg). Moreover, the effect of clonidine (50μg/kg) was prevented by yohimbine (5 mg/kg) or idazoxan (1 mg/kg). Haloperidol (50 μg/kg) or propranolol (10 mg/kg) did not affect evoked noradrenaline release while prazosin (0.05–1 mg/kg) induced a moderate increase. However, prazosin did not prevent the effect of clonidine (50 μg/kg). Reserpine (5 mg/kg) pretreatment for l h induced a pronounced decrease in the evoked noradrenaline release and abolished the effect of yohimbine (2 mg/kg). Pretreatment by desipramine 30 min before injection abolished the effect of clonidine (50μg/kg) but not of yohimbine (2 mg/kg). The amplitude of the yohimbine (2 mg/kg) effect depended on the frequency of the stimulation: it was maximal between 3 and 7 Hz and gradually declined from 10 to 20 Hz. These results show that noradrenaline release is presynaptically controlled by an alpha-2 adrenoreceptor and suggest that, in physiological conditions, endogenous extracellular noradrenaline inhibits its own phasic release. In conclusion, noradrenergic terminals act as a high pass filter which converts impulse flow into noradrenaline release and the features of this filter are modulated by extracellular noradrenaline via an alpha-2 adrenoreceptor.