title: 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 paraventricular 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 20s 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 micrograms/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 (50 micrograms/kg) was prevented by yohimbine (5 mg/kg) or idazoxan (1 mg/kg). Haloperidol (50 micrograms/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 micrograms/kg). Reserpine (5 mg/kg) pretreatment for 1 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 (50 micrograms/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.
authors.affiliation: INSERM U 171 and CNRS UA 1195, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
authors.forename: C
authors.initials: C
authors.lastname: Mermet
authors.forename: M F
authors.initials: MF
authors.lastname: Suaud-Chagny
authors.forename: F
authors.initials: F
authors.lastname: Gonon
mesh_terms: D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine