Desensitization of α₂-Adrenoceptors which Regulate Noradrenaline Synthesis and Release after Chronic Treatment with Clorgyline in the Rat Brain

Abstract

The sensitivity of α₂-adrenoceptors which regulate synthesis and release of noradrenaline was investigated in hippocampus, parietal cortex, and hypothalamus of rats treated with clorgyline. After administering a DOPA decarboxylase inhibitor, the in vivo tyrosine hydroxylase activity and the noradrenaline content were evaluated. Acute and chronic treatment with clorgyline led to both increases of noradrenaline levels and decreases of tyrosine hydroxylase activity, determined as the accumulation of DOPA. Whereas the α₂-adrenoceptor agonist clonidine induced a similar reduction in tyrosine hydroxylase activity in the group subjected to the acute treatment and in the control group, it failed to do so after chronic clorgyline treatment. In hippocampal and cortical synaptosomes, a reduction in the sensitivity of α₂-adrenoceptors which regulate [³H]noradrenaline release, reflected by the shift to the right of the concentration-effect curves for oxymetazoline, was also found after the repeated treatment. These results indicate a desensitization of α₂-adrenoceptors after chronic treatment with clorgyline.

Monoamine Oxidase A Activity and Norepinephrine Level in Hippocampus Determine Hyperwheel Running in SPORTS Rats

“…These a 2 -ARs bind NE and decrease the release of NE from the presynaptic neurons resulting in a decrease of postsynaptic AR stimulation (Shishikina et al, 2004;Lahdesmaki et al, 2003;Roberto and Silvio, 2004;Heck and Bylund, 1998). Thus, the blockade of presynaptic a 2 -ARs with yohimbine should increase extracellular NE concentration (Galeotti et al, 2004;Prieto and Giralt, 2002). In the present study, the extracellular NE levels were already high in SPORTS rat hippocampus even in the absence of yohimbine (Figure 2a).…”

“…The NE exerts its effects through its receptors (LeDoux, 1994;Cryan et al, 2004;Roberto and Silvio, 2004). Prolonged NE stimulation causes downregulation of its receptors (Prieto and Giralt, 2002). Thus, elevated extracellular NE was expected to alter the population of ARs in the hippocampus of SPORTS rats.…”

Determination of serotonin, noradrenaline, dopamine and their metabolites in rat brain extracts and microdialysis samples by column liquid chromatography with fluorescence detection following derivatization with benzylamine and 1,2-diphenylethylenediamine

“…The corresponding extracellular levels of 5-HIAA and DOPAC decreased to 83 and 41%, respectively. Several earlier microdialysis studies using the LCEC methods [43,[46][47][48][49] have demonstrated that MAO-A and MAO-B inhibitors cause increases in extracellular DA, NA and 5-HT levels, whereas the metabolites DOPAC and 5-HIAA were decreased. Thus, clorgyline caused significant decreases in extracellular levels of deaminated metabolites and increase in DA both after a single [50,51] or repeated [52] administration.…”