RELATIONSHIP BETWEEN TYROSINE-HYDROXYLASE CONTENT AND NORADRENERGIC CELL REACTIVITY TO PIPEROXANE - AN IN-VIVO VOLTAMMETRIC APPROACH IN THERAT LOCUS-CERULEUS

A previous electrochemical study showed that the increase in the tyros ine hydroxylase (TH) content of the locus coeruleus (LC) produced by R U24722 administration was associated with a relative decrease in the c atecholaminergic metabolic reactivity of this nucleus to a hypotensive stimulus. SinCe alpha2 receptors participate in the regulation of the activity of both LC neurons and TH, the aim of the present work was t o evaluate the possible involvement of the autoinhibition mediated by alpha2 autoreceptors in the inverse relationship between the reactivit y of the LC and its TH content. Our study was divided into two success ive steps: (i) the electrochemical measurement of the in vivo metaboli c activation of LC cells in response to alpha2-adrenergic receptor blo ckade, and (ii) the evaluation of the quantity of TH every 100 mum alo ng the caudorostral axis in each recorded LC. The capacity of TH prote in to be activated was evaluated by the measurement, using differentia l normal pulse voltammetry, of the in vivo variations of the extracell ular 3,4-dihydroxyphenylacetic acid concentrations in response to six cumulated doses of the alpha2-antagonist piperoxane. The corresponding dose-response curves, determined in control- and RU24722-treated rats , were expressed as a function of the quantity of TH contained either in the whole recorded LC or in the 100 mum-wide coronal interval surro unding the recording site. It was established that the slopes of the d ose - response curves were significantly (P < 0.01) and inversely rela ted to the quantity of TH at the level of the recording site. This res ult suggests that the negative control of the catecholaminergic metabo lic reactivity in a restricted area of the LC could be directly or ind irectly dependent on the level of expression of TH protein in this par ticular area.