Decrease in the Reactivity of Locus Coeruleus Neurons to Hypotension after an Increase in their Tyrosine Hydroxylase Content: A Subregional In Vivo Voltammetry Study in the Rat

Abstract

The aim of the present work was to determine if noradrenergic neurons of the anterior and the posterior subregions of the locus coeruleus exhibit a difference in reactivity in response to sodium nitroprusside-induced arterial hypotension, and if the pharmacological induction of tyrosine hydroxylase by RU24722 modifies the reactivity of locus coeruleus neurons to this hypotensive stimulus. Previous findings have demonstrated that administration of RU24722 increases the concentration of tyrosine hydroxylase in the rat locus coeruleus by two different mechanisms in the anterior and in the posterior locus coeruleus subregions. The goal of the present study was to measure in vivo the changes in catecholaminergic metabolism in the locus coeruleus after treatment with RU24722 using differential normal pulse voltammetry (DNPV). In vehicle-treated rats, arterial hypotension increased catecholaminergic metabolism with the same pattern in the two locus coeruleus subregions. However, the changes in the magnitude of the catechol oxidation current throughout the recording period were significantly smaller in the posterior subregion (P < 0.001). In the RU24722-pretreated rats, there was a 39% increase in tyrosine hydroxylase and dihydroxyphenylacetic acid in the locus coeruleus. The functional reactivity to hypotension measured by DNPV was significantly decreased (P < 0.001) in both the anterior and posterior locus coeruleus subregions with RU24722 treatment. Therefore, this study suggests that the response of locus coeruleus cells to a hypotensive stimulus depends upon the intracellular tyrosine hydroxylase concentration both in the basal condition and during pharmacological induction of tyrosine hydroxylase gene expression.

Long-lasting adverse effects of prenatal hypoxia on developing autonomic nervous system and cardiovascular parameters in rats

“…In contrast, the locus coeruleus reacted to prenatal hypoxia by a sustained increase in metabolic activity until 9 weeks and a normalization of the noradrenaline synthesis later at adulthood. Given that the A6 region is involved in haemodynamic regulation [33] and is considered as an inhibitory regulatory structure for the sympathetic outflow [16], the altered maturation of A6 might contribute to the lowered autonomic nervous system activity seen in key sympathetic structures at 3 and 9 weeks of age. In addition, these transient central events occurring during development might be involved in the long-term disturbed autonomic nervous system activity in adult.…”

Comparison of effects of hypotension and handling stress on the release of noradrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat

“…It is generally assumed that DOPAC in the LC reflects the functional state of LC noradrenergic neurons (Ortemann et al 1993;Vachette et al 1993). The present data show few similarities in changes of noradrenaline and DOPAC in the LC.…”

Relationship Between Tyrosine Hydroxylase Content and Noradrenergic Cell ‐Reactivity to Piperoxane: an In Vivo Voltammetric Approach in the Rat Locus Coeruleus

“…A carbon fibre microelectrode was treated and tested in vitro as described previously Vachette et al, 1993). The electrode…”

“…Electrochemical signals obtained were quantified by measuring the height of the oxidation peaks and were expressed as percentages of baseline peak height value as described previously (Vachette et al, 1993). Data are expressed as mean f SEM.…”