Brain noradrenergic neuronal activity affects 3,4-dihydroxyphenylethyleneglycol (DHPG) levels
Abstract
Brain regional DHPG levels were determined following pharmacological manipulations that are known to alter brain noradrenergic neuronal activity. In rats given the α-adrenergic antagonist yohimbine (1, 5 and 10 mg/kg, i.p.) 2 h prior to sacrifice, there was a dose-dependent increase in cortical, midbrain, pons + medulla, hypothalamic and spinal total DHPG and MHPG concentrations. In contrast, cortical and spinal total DHPG and MHPG concentrations were markedly decreased 2 h following the α-adrenergic agonist, clonidine (10 and 250 μg/kg, i.p.). These findings indicate that rat brain DHPG formation is also sensitive to changes in brain noradrenergic neuronal impulse flow.
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Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study
2023, Neuroscience LettersMonoaminergic systems are known to be involved in the pathophysiology of neuropsychiatric disorders and vegetative functions due to their established influence on hypothalamic and subcortical areas. These systems can be modulated by lifestyle factors, especially exercise, which is known to produce several beneficial effects on reproduction, brain health, and mental disorders. The fact that exercise is sensed by the brain shows that muscle-stimulated secretion of myokines allows direct crosstalk between the muscles and the brain. One of such exercise-induced beneficial effects on the brain is exhibited by irisin—a recently discovered PGC-1α-dependent adipo-myokine mainly secreted from skeletal muscle during exercise. Thus, we hypothesized that irisin may affect central monoamine levels and thus play an important role in the muscle–brain endocrine loop. To test this assertion, for 10 weeks, vehicle (deionized water) or 100 ng/kg irisin was injected intraperitoneally once a day to 12 male and 12 female rats after which the levels of monoamines and their metabolites were determined by HPLC-ECD. In the hypothalamic nuclei, irisin significantly decreased dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) (p < 0.05), DOPAC/DA ratio (p < 0.01) and noradrenaline (NA, p < 0.05) levels in the anteroventral periventricular nucleus (AVPV), and DOPAC and NA levels in the medial preoptic area (mPOA) (p < 0.05), having a crucial role in reproduction and sexual motivation, respectively. On the other hand, irisin significantly increased DOPAC levels in the lateral hypothalamic area (LHA) (p < 0.05), which acts as a hunger center, while it significantly decreased the levels of DA, NA, and its metabolite 3,4-dihydroxyphenylglycol (DHPG) in the ventromedial hypothalamic nucleus (VMH) as a known satiety center (p < 0.05). In nucleus accumbens (NaC), irisin significantly reduced 5-hydroxyindoleacetic acid (5-HIAA) levels (p < 0.05), which are implicated in autism spectrum disorder (ASD) physiopathology. It also significantly increased DA levels in this area, thus exhibiting positive effects on depression and sexual dysfunction in men. On the other hand, it significantly decreased serotonin (5-HT) (p < 0.01) and its metabolite 5-HIAA levels in the medial amygdala (MeA) (p < 0.05), indicating that it may play a role in social behaviors. Moreover, it significantly attenuated NA levels in the same subcortical area (p < 0.01), which is directly involved in stress-induced activation of the central noradrenergic system. These findings demonstrate for the first time that irisin induces significant changes in monoamine levels in many hypothalamic nuclei involved in feeding behavior and vegetative functions, as well as in subcortical nuclei related to neuropsychiatric disorders.
Determination of 3,4-dihydroxyphenyl glycol in plasma by gas chromatography-mass spectrometry and high-performance liquid chromatography methods
1996, Journal of Chromatography B: Biomedical ApplicationsSeveral modifications of GC-MS and HPLC methods for plasma level DHPG have been described. The effects of storage temperature and stabilizing agents on DHPG stability have been studied. The stabilizing agent has been found to play a more important role than low-temperature storage in preventing DHPG from decomposition during sample storage. A specific and sensitive GC-MS method (electron impact) has been established using stable isotope-labeled DHPG as an internal standard. HPLC has been improved by modifying the conditions, resulting in a good separation of DHPG and internal standard from solvent front and other early eluting compounds. Comparison of the GC-MS and HPLC procedures demonstrates a strong correlation between these two methods.
A role for central postsynaptic α<inf>2</inf>-adrenoceptors in glucoregulation
1991, Brain ResearchCentral or peripheral administration of theα2-adrenoceptor agonist clonidine causes marked hyperglycemia in the rat. It is not clear whether this effect is mediated within the brain at either pre- or postsynapticα2-adrenoceptors or whether it is due to peripheralα2-agonist actions. We employed computerized mass spectrometry to measure noradrenaline (NA) and its primary neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) in the medial basal hypothalamus of rats treated acutely with clonidine, theα2-antagonist yohimbine, the postganglionic noradrenergic blocker guanethidine and the neuroglycopenic agent 2-deoxy-d-glucose (2-DG). That clonidine's hyperglycemic effect was due, in part, to an action at centralα2-adrenoceptors was indicated by the ability of guanethidine to significantly inhibit the glucose response. Because of clonidine's inhibition of hypothalamic NA release (assessed by the DHPG/NA ratio), presumably by presynaptic agonism, these data indicated that postsynaptic receptor stimulation by clonidine was involved in activating glucose release. Yohimbine markedly increased the hypothalamic DHPG/NA ratio, reflecting presynaptic stimulation of NA release, but at the same time inhibited the hyperglycemic response due to 2-DG administration. This latter effect to block hyperglycemia is consistent with antagonism of postsynapticα2-adrenoceptors involved in mediating hepatic glucose output. These data indicate a major role for postsynapticα2-adrenoceptors in glucoregulation.
Anxiogenic β-carboline FG 7142 produces activation of noradrenergic neurons in specific brain regions of rats
1991, Pharmacology, Biochemistry and BehaviorBy measuring the levels of two major metabolites of rat brain noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), we investigated the effects of anxiogenic β-carboline FG 7142, an inverse agonist of benzodiazepine (BZD) receptors, on brain noradrenergic activity of rats. Thirty min after treatment with FG 7142 (15 mg/kg, IP), levels of both MHPG and DHPG in the hypothalamus, amygdala and thalamus, but not in the hippocampus and cerebral cortex, significantly increased. These increases were significantly antagonized by pretreatment with BZD receptor antagonist Ro 15-1788 (15 mg/kg, IP). Sixty min after treatment with FG 7142 at the same dose, significant increases in both metabolite levels occured in the hypothalamus, amygdala, thalamus and cerebral cortex, and increases in MHPG levels only were observed in the hippocampus. These increases were significantly blocked by pretreatment with α2-adrenoceptor agonist clonidine (100 μg/kg, IP). The present findings suggest that FG 7142 can produce increases in brain noradrenergic activity in specific brain regions by interacting with BZD receptors, and may support the hypothesis that hyperactivity of brain noradrenergic systems may be one neural mechanism in provocation of aversive emotional changes (anxiety, fear or panic).
Involvement of dopamine in the central effect of neurotensin on intestinal motility in rats
1990, PeptidesThe effects of intracerebroventricular (ICV) administration of neurotensin (NT) before a meal on intestinal postprandial motility were examined in conscious rats chronically fitted with intraparietal Nichrome electrodes in the duodeno-jejunum. The effects were compared with those of two analogues, [D-Tyr11]NT and [D-Trp11]NT, resistant to degradation by brain peptidases. NT (10 μg ICV) delayed the occurrence of postprandial disruption of duodenal motility and blocked it on the jejunum. [D-Tyr11]NT and [D-Trp11]NT (1 μg ICV) elicited the same effects but at a ten-fold lower dose. NT administered peripherally just before a meal significantly lengthened the duration of the postprandial motor pattern. The central effect of NT on the fed pattern involved dopaminergic neurons as it was mimicked by dopamine, blocked by haloperidol and partly antagonized by either sulpiride or (+) SCH 23390. It is concluded that: 1) both D1 and D2 receptors are involved in the blocking effect of the postprandial disruption induced by central NT; 2) that [D-Tyr11]NT and [D-Trp11]NT are potent agonists at NT receptors in the brain.
Unchanged regional norepinephrine glycol metabolite levels in rat brain two months after amygdala kindling
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