In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism

Brannan, Timothy; Prikhojan, A.; Martinez-Tica, J.; Yahr, Melvin D.

doi:10.1007/bf02251224

Cited by 36 publications

(22 citation statements)

References 30 publications

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“…However, if CORT is inhibiting DA metabolism, this inhibition is not sufficient to provide enough regulatory feedback to produce corresponding changes in DA synthesis or turnover. In support of this possibility, basal extracellular DA concentrations remain stable with selective inhibition of MAO-B (Brannan et al 1995). CORT also inhibits peripheral catecholamine metabolite concentrations, similar to the decrease in central DA utilization observed here.…”

Section: Discussionsupporting

confidence: 81%

Glucocorticoid Effects on Mesotelencephalic Dopamine Neurotransmission

Lindley

1999

Neuropsychopharmacology

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Multiple neurochemical estimates were used to examine peripheral corticosterone (CORT) effects in dopaminergic terminal regions. Acute CORT administration, which elevated plasma CORT (5 h), slightly decreased dihydroxyphenylacetic acid (DOPAC) to dopamine (DA) ratios in the striatum but not in other regions examined. Two weeks of adrenalectomy (ADX) increased both medialAdverse environmental stimuli evoke a number of physiological responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and ascending catecholaminergic neurons. Although these responses are critical to an organism's ability to adapt metabolically and behaviorally to stressful events, it has also been hypothesized that sustained alterations in these systems may underlie the pathophysiology of some psychiatric disorders (Dinan 1996;Nemeroff 1993;Piazza and Le Moal 1996;Schatzberg et al. 1985). For example, the cognitive disturbances in psychotic depressed patients may be secondary to the effect of HPA axis alterations on central dopaminergic neuronal activity (Schatzberg and Rothschild 1988;Schatzberg et al. 1985;Wolkowitz 1994).In support of adrenal steroids influencing dopamine (DA) neurotransmission, a number of behaviors believed to be associated with dopaminergic neurons are influenced by corticosterone (CORT). For example, glucocorticoids attenuate D 2 receptor agonist-induced behaviors (Cador et al. 1993;Cools and Peeters 1992;Faunt and Crocker 1988;Faunt and Crocker 1989). In addition, glucocorticoids facilitate stimulant self-administration and stimulant-induced locomotor activity (Marinelli et al. 1994;Ortiz et al. 1995;Patacchioli et al. 1997;Piazza et al. 1993;Rivet et al. 1989) stress-induced sensitization of extracellular DA release by cocaine (Rouge-Pont et al. 1995).Furthermore, indirect biochemical data support the hypothesis that adrenal steroids modulate these behaviors through an influence on mesotelencephalic DA neurotransmission. In vitro, CORT regulates tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis (reviewed in Meyer 1985). For example, the glucocorticoid receptor agonist dexamethasone increases TH expression in both PC12 cells (Baetge et al. 1981;Lewis et al. 1983) and the adrenal medulla (Stachowiak et al. 1988). In addition, CORT increases the rate of tyrosine phosphorylation in the ventral tegmental area, containing the mesocortical and mesolimbic perikarya (Nestler et al. 1989). Moreover, 50% of mesocortical, mesolimbic, and nigrostriatal perikarya (A8-A10) are immunoreactive for type II glucocorticoid receptors (Harfstrand et al. 1986). However, previous in vivo studies directly investigating the effects of CORT on DA neurochemical estimates of neuronal activity have produced apparently conflicting results. For example, CORT has been observed to increase, decrease, or not alter DA utilization and extracellular DA release (Dunn 1988;Imperato et al. 1992;Inoue and Koyama 1996;Rothschild et al. 1985;Tanganelli et al. 1990;Thomas et al. 1994;Wolkowitz et al. 1986). The present s...

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Section: Discussionsupporting

confidence: 81%

Glucocorticoid Effects on Mesotelencephalic Dopamine Neurotransmission

Lindley

1999

Neuropsychopharmacology

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“…Brannan et al (13) and Kaseda et al (14) demonstrated that selegiline treatment in rats and primates markedly increases DA level in dialysates after L-DOPA treatment. These studies confirm the usefulness of selegiline as an adjunct to L-DOPA, but also suggest the difficulty in deciding the clinical dose of L-DOPA for selegiline-treated patients for maintaining brain DA level in a safe level between the therapeutic threshold and the adverse reaction threshold.…”

Section: Discussionmentioning

confidence: 99%

Effects of Subchronic Treatment With Selegiline on L-DOPA-Induced Increase in Extracellular Dopamine Level in Rat Striatum

et al. 2006

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Abstract. Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/ or selegiline using a microdialysis method. Rats given 10 mg / kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg / kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.

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“…The data with clorgyline recall that MAO A is mainly involved in the regulation of the dopaminergic system in the striatum [13][14][15][16][17][18] , but, elsewhere, its role in the metabolism of DA and of 5-HT is region-dependent 8,16 . The lack of effect of clorgyline on NE tissue content is not surprising because it usually requires higher non-selective doses or chronic treatment to have a pronounced effect.…”

Section: Resultsmentioning

confidence: 94%

Comparative Analysis of the Neurochemical Profile and MAO Inhibition Properties of N-(Furan-2-ylmethyl)-N-methylprop-2-yn-1-amine

Deurwaerdère

Binda

Corne

et al. 2016

ACS Chem. Neurosci.

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The regulation of brain monoamine levels is paramount for cognitive functions and the enzymes monoamine oxidases (MAO A and B) play a central role in these processes. The aim of this study was to evaluate whether the pro-cognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) were related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both the classic MAO A or MAO B inhibitors clorgyline and L-deprenyl, respectively. Although all the inhibitors (1 and 4 mg/kg) increased cortical serotonin tissue content, only F2MPA increased the levels of cortical noradrenaline. In the striatum, clorgyline (1 mg/kg), but not F2MPA (1 mg/kg), reduced extracellular levels of dopamine metabolites at rest or stimulated by the intrastriatal application of the MAO substrate 3-methoxytyramin. In vitro, F2MPA exhibited a low affinity toward MAO B and MAO A. Nonetheless, it modified the B form of MAO, forming a flavin adduct structurally similar to that with deprenyl. F2MPA was rapidly metabolized in the presence of rat, but not human, microsomes, producing a hydroxylated derivative. In conclusion, the effect of F2MPA on cognition may arise from monoaminergic changes in the cortex, but the role of MAO in this process is likely to be negligible, consistently to the F2MPA poor affinity for MAO.

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In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism

Cited by 36 publications

References 30 publications

Glucocorticoid Effects on Mesotelencephalic Dopamine Neurotransmission

Glucocorticoid Effects on Mesotelencephalic Dopamine Neurotransmission

Effects of Subchronic Treatment With Selegiline on L-DOPA-Induced Increase in Extracellular Dopamine Level in Rat Striatum

Comparative Analysis of the Neurochemical Profile and MAO Inhibition Properties of N-(Furan-2-ylmethyl)-N-methylprop-2-yn-1-amine

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