Differential effects of NMDA and non-NMDA antagonists on the activity of aromatic l-amino acid decarboxylase activity in the nigrostriatal dopamine pathway of the rat

Fisher, Andrew; Biggs, C.S.; Starr, Michael S.

doi:10.1016/s0006-8993(98)00129-2

Cited by 36 publications

(22 citation statements)

References 40 publications

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“…Similar responses to dopamine receptor ligands have also been observed in various rodent brain regions (Zhu et al, 1992(Zhu et al, , 1993Hadjiconstantinou et al, 1993;Cho et al, 1997Cho et al, , 1999Neff et al, 2006). Regulation of AADC by serotonergic receptors (Neff et al, 2006) and Nmethyl-D-aspartate (NMDA) glutamatergic receptors (Hadjiconstantinou et al, 1995;Fisher et al, 1998) has also been reported. There is also some evidence for AADC regulation associated with systemic lupus erythematosus (Bengtsson et al, 2016), Parkinson' disease (Gjedde et al, 1993), and schizophrenia (Reith et al, 1994).…”

Section: Vertebrate Trace Aminessupporting

confidence: 57%

Trace Amines and Their Receptors

Gainetdinov¹,

Hoener²,

Berry³

2018

Pharmacol Rev

280

287

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Section: Vertebrate Trace Aminessupporting

confidence: 57%

Trace Amines and Their Receptors

Gainetdinov¹,

Hoener²,

Berry³

2018

Pharmacol Rev

280

287

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“…), and memantine and amantadine (40 mg/ kg, i.p.) increased the activity of DDC by factors of 2-9 in vitro in homogenates from striatum and substantia nigra of rat (Fisher et al, 1998). Finally, we recently reported that DDC activity in vivo in rat striatum was increased four-fold after sub-chronic treatment (8 days) with dizocilpine (0.2 mg/kg/day, i.p.…”

Section: Introductionmentioning

confidence: 95%

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine

Deep

Sadikot

Gjedde

et al. 1999

Synapse

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The efficacy of amantadine in alleviating motor symptoms of Parkinson's disease may be mediated in part by stimulation of cerebral dopa decarboxylase (DDC) activity, secondary to antagonism of N-methyl-D-aspartate (NMDA) type glutamate receptors. We tested the specific hypothesis that amantadine increases the decarboxylation rate of 6-[(18)F]fluoro-L-DOPA (FDOPA), an exogenous substrate for DDC, in healthy human brain. Radioactivity concentrations in brain tissue of neurologically normal volunteers (n = 5) injected intravenously with FDOPA ( approximately 4.5 mCi) were recorded by positron emission tomography (PET) for 120 min, first in a baseline condition, and again following three consecutive days of treatment with amantadine (100 mg/day, p.o.). Data from four telencephalic regions of interest containing appreciable DDC activity were analyzed with the tissue slope-intercept plot, using cerebellar cortex as the reference tissue, to estimate a coefficient of in situ FDOPA decarboxylation (k(3)(r), min(-1)). Mean estimates of k(3)(r) were increased following amantadine treatment in caudate nucleus (+12%), putamen (+28%), ventral striatum (+27%), and frontal cortex (+9%). For an initial confidence level of 95%, paired one-sided Student's t-tests with Bonferroni correction for multiple comparisons revealed a statistically significant drug effect in ventral striatum. Present results are consistent with stimulation of DDC activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine, and suggest that this response is an important mechanism underlying the anti-parkinsonian properties of amantadine. Nonetheless, PET studies in parkinsonian patients using higher, clinically effective doses of amantadine may reveal more pronounced enhancements of cerebral DDC activity.

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“…Physiological stimuli (Hadjiconstantinou et al, 1988), neurotransmitter receptors (Rossetti et al, 1989(Rossetti et al, , 1990Zhu et al, 1992;Hadjiconstantinou et al, 1993Hadjiconstantinou et al, , 1995Cho et al, 1997;Fisher et al, 1998) and second messenger systems (Young et al, 1998) participate in the regulation of enzyme activity. In nigrostriatal neurons, dopamine appears to regulate AAAD via D1-and D2-like receptors.…”

Section: Introductionmentioning

confidence: 99%

“…AAAD is not considered to be the rate-limiting enzyme for catecholamine or indoleamine synthesis; however, it is the rate-limiting step for the synthesis of trace amines and becomes rate-limiting for dopamine formation in Parkinson's disease patients treated with L-DOPA. AAAD is a regulated enzyme, and accumulated evidence suggests that its activity in the rodent brain is tuned by short-and long-term mechanisms that apparently involve enzyme activation and induction.Physiological stimuli (Hadjiconstantinou et al, 1988), neurotransmitter receptors (Rossetti et al, 1989(Rossetti et al, , 1990Zhu et al, 1992;Hadjiconstantinou et al, 1993Hadjiconstantinou et al, , 1995Cho et al, 1997;Fisher et al, 1998) and second messenger systems (Young et al, 1998) participate in the regulation of enzyme activity. In nigrostriatal neurons, dopamine appears to regulate AAAD via D1-and D2-like receptors.…”

mentioning

confidence: 99%

Clozapine Modulates Aromatic l-Amino Acid Decarboxylase Activity in Mouse Striatum

Neff¹,

Wemlinger²,

Duchemin³

et al. 2006

J Pharmacol Exp Ther

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Clozapine is efficacious for treating dopaminergic psychosis in Parkinson's disease and ameliorates L-DOPA-induced motor complications. Based on its pharmacology and reported enhancing effects on dopamine metabolism and tyrosine hydroxylase activity, we investigated whether it could modulate the activity of aromatic L-amino acid decarboxylase (AAAD), the second enzyme for the biosynthesis of catecholamines and indoleamines. A single dose of clozapine increased AAAD activity of striatum in a dose-and time-dependent manner. At 1 h, enhanced enzyme activity was characterized by an increased V max for substrate and cofactor and was accompanied by elevated levels of protein in striatum and mRNA in substantia nigra, ventral tegmental area, locus coeruleus, and raphe nuclei. Acute clozapine increased tyrosine hydroxylase activity in striatum but with differing temporal patterns from AAAD and heightened dopamine metabolism. Interestingly, the response of the dopaminergic markers to clozapine was greater following a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion. Chronically administered clozapine increased AAAD activity and protein and dopamine metabolism in striatum without affecting tyrosine hydroxylase. Exogenous L-DOPA decarboxylation was accelerated in the striatum of intact and MPTPlesioned mice following acute clozapine, and the effect was exaggerated in the MPTP mice. To identify receptors involved, antagonists of receptors occupied by clozapine were employed. D4, 5-HT1 A , and 5-HT2 A , in addition to D1, D2, and D3, antagonists, augmented AAAD activity in striatum, whereas 5-HT2 C , 5-HT3, muscarinic, and ␣-1 and ␣-2 adrenergic antagonists were ineffective. For the first time, these studies provide evidence that clozapine modulates AAAD activity in the brain and suggests that dopamine and serotonin receptors are involved.Aromatic L-amino acid decarboxylase (AAAD) is a ubiquitous enzyme essential for the formation of catecholamines, indoleamines, and trace amines (Berry et al., 1996). AAAD is not considered to be the rate-limiting enzyme for catecholamine or indoleamine synthesis; however, it is the rate-limiting step for the synthesis of trace amines and becomes rate-limiting for dopamine formation in Parkinson's disease patients treated with L-DOPA. AAAD is a regulated enzyme, and accumulated evidence suggests that its activity in the rodent brain is tuned by short-and long-term mechanisms that apparently involve enzyme activation and induction.Physiological stimuli (Hadjiconstantinou et al., 1988), neurotransmitter receptors (Rossetti et al., 1989(Rossetti et al., , 1990Zhu et al., 1992;Hadjiconstantinou et al., 1993Hadjiconstantinou et al., , 1995Cho et al., 1997;Fisher et al., 1998) and second messenger systems (Young et al., 1998) participate in the regulation of enzyme activity. In nigrostriatal neurons, dopamine appears to regulate AAAD via D1-and D2-like receptors. Indeed, acute blockade of dopamine D1-like receptors with SCH23390 and of dopamine D2-like receptors with haloperidol, ...

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Differential effects of NMDA and non-NMDA antagonists on the activity of aromatic l-amino acid decarboxylase activity in the nigrostriatal dopamine pathway of the rat

Cited by 36 publications

References 40 publications

Trace Amines and Their Receptors

Trace Amines and Their Receptors

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine

Clozapine Modulates Aromatic l-Amino Acid Decarboxylase Activity in Mouse Striatum

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