Interactions between dopamine and γ-aminobutyrate in the substantia nigra: Implications for the striatonigral output hypothesis

Starr, Michael S.; Summerhayes, M.; Kilpatrick, Ian C.

doi:10.1016/0306-4522(83)90198-7

Cited by 44 publications

(8 citation statements)

References 48 publications

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“…Interestingly, reduction of VMTh GABA release induced by TTX was associated with attenuation of akinesia. This is consistent with our previous finding that SNr perfusion of higher TTX concentrations (10 M) evoked contralateral rotations in naive rats (Morari et al, 1996) and strengthens the view that inhibition of nigrothalamic GABAergic neurons results in disinhibition of locomotion (Starr et al, 1983;Deniau and Chevalier, 1985). Nigrothalamic GABAergic neurons express GABA A receptors (Nicholson et al, 1995), which drive both tonic (Rick In the same rats, akinesia was evaluated (every 15 min for up to 180 min) by using the bar test separately at the contralateral (C) and ipsilateral (D) paws (described in Materials and Methods).…”

Section: Neurobiological Substrates Underlying J-113397/l-dopa Interasupporting

confidence: 93%

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Marti¹,

Trapella²,

Viaro³

et al. 2007

J. Neurosci.

126

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By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6-hydroxydopamine hemilesioned rats (Marti et al., 2005). We now present evidence that coadministration of the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol-2-one (J-113397) and L-DOPA to 6-hydroxydopamine hemilesioned rats produced an additive attenuation of parkinsonism. To investigate the neurobiological substrates underlying this interaction, in vivo microdialysis was used in combination with behavioral measurements (bar test). J-113397 and L-DOPA alone reduced the time on bars (i.e., attenuated akinesia) and elevated GABA release selectively in the lesioned substantia nigra reticulata. J-113397 also reduced nigral glutamate levels, whereas L-DOPA was ineffective. J-113397 and L-DOPA coadministration produced additive antiakinetic effect, which was associated with additive increase in nigral GABA release but no additional reductions in glutamate levels. To investigate whether the increase in nigral GABA release could translate to changes in nigrothalamic transmission, GABA release was monitored in the ventromedial thalamus (one of the main target areas of the nigrothalamic projections). J-113397 and L-DOPA decreased thalamic GABA release and attenuated akinesia, their combination resulting in a more profound effect. These actions were prevented by perfusing the voltage-dependent Na ϩ channel blocker tetrodotoxin or the GABA A receptor antagonist bicuculline in the substantia nigra reticulata. These data demonstrate that J-113397 and L-DOPA exert their antiparkinsonian action through overinhibition of nigrothalamic transmission and suggest that NOP receptor antagonists may be useful as an adjunct to L-DOPA therapy for Parkinson's disease.

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Section: Neurobiological Substrates Underlying J-113397/l-dopa Interasupporting

confidence: 93%

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Marti¹,

Trapella²,

Viaro³

et al. 2007

J. Neurosci.

126

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“…These results are consistent with the hypothesis that stimulation of D1 receptors in SNR contributes significantly to the behavioral activation associated with increased dopaminergic transmission in basal ganglia (Asin and Montana, 1988;LaHoste and Marshall, 1990;Robertson and Robertson, 1987;Yurek and Hipkens, 1993). Furthermore, the present findings provide additional elements of support for a model in which phasic &sinhibition of thalamocortical activity, secondary to enhanced GABAergic inhibition of nigrothalamic output neurons, is an important mechanism by which dendritic DA release and subsequent nigral D1 receptor stimulation can exert behaviorally relevant effects (Cameron and Williams, 1993;Chevalier and Deniau, 1990;Gauchy et al, 1987;Starr et al, 1983).…”

Section: Discussionsupporting

confidence: 65%

“…The striatonigral termination upon SNR output neurons appears to be quantitatively the more significant . (Nitsch and Riesenberg, 1988;Williams and Faull, 1985) and it has been proposed that many of the behavioral effects of stimulation of striatal DA receptors are translated, via this pathway, into an apparent inhibition of GABAergic SNR output neurons (Amt and Scheel-Kriiger, 1979;Fletcher and Starr, 1987;Herrera-Marschitz and Un-gerstedt, 1984;Morelli et al, 1980;Olianas et al, 1978;Starr et al, 1983). Inhibition of the GABAergic SNR projection to the ventromedial (VM) nucleus of the thalamus (Di Chiara et al, 1979;Faull and Mehler, 1978;Fibiger et al, 1972;Herkenham, 1979) is, in turn, thought to elicit a functionally important disinhibition of thalamocortical activity (Chevalier and Deniau, 1990;Deniau and Chevalier, 1985;Deniau et al, 1976).…”

Section: Introductionmentioning

confidence: 99%

Amphetamine-induced release of dendritic dopamine in substantia nigra pars reticulata: D1-mediated behavioral and electrophysiological effects

Timmerman¹,

Abercrombie²

1996

Synapse

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Dopamine (DA) released from dendrites of substantia nigra dopaminergic neurons potentially is in a position to modulate basal ganglia outputs from the substantia nigra pars reticulata (SNR) via stimulation of D1 receptors on the terminals of striatonigral afferents. The effects of endogenous DA release in the SNR were examined in rats using behavioral activation, multiunit activity of SNR neurons, and cortical EEG pattern as dependent measures. Unilateral infusion of amphetamine (AMPH) into SNR (10 micrograms/0.5 microliter; 5 min) produced a short-lasting behavioral activation that was blocked by coinfusion of the D1 DA receptor antagonist SCH 23390 (0.5 micrograms). Multiunit recordings of SNR neurons in anesthetized rats showed that AMPH, infused as above, produced a rapid decrease in SNR activity. This decrease was maximal (approximately 90%) during the first 10 min postinfusion, followed by a gradual return to baseline levels. Coinfusion of SCH 23390 blocked the AMPH-induced decrease in SNR activity, although by itself this drug produced a 40% decrease in activity. Cortical EEG acquired during the SNR infusions/recordings showed a short-duration change in pattern immediately after AMPH infusion. A relative shift in power from the lowest frequency interval determined (0.8-2.7 Hz) to the next higher frequency interval (2.7-6.8 Hz) was observed which could be prevented by coinfusion of SCH 23390. Thus, dendritically released DA can inhibit the activity of SNR neurons via local stimulation of D1 receptors. This effect is associated with a brief behavioral activation and EEG desynchronization.

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“…Alternatively, D2 receptors may be present on GABA-containing nigral projection neurones (e.g., nigrothalamic, nigrotectal, or nigroreticular) and decrease GABA output from a quite separate, smaller, and more metabolically active pool of the amino acid (Starr et al, 1983). Although lesion studies have emphasised D2 ligand binding and dopamine-stimulated adenylate are separately localised in the nigra, they do not rule out the possibility that D2 receptors are situated on nondopaminergic elements (Murrin et al, 1979;Reisine et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Opposing Roles of Dopamine D₁ and D₂ Receptors in Nigral γ‐[³H]Aminobutyric Acid Release?

Starr

1987

Journal of Neurochemistry

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This study examined the effects of dopamine D1 and D2 receptor agonists and antagonists on the spontaneous and calcium-dependent, K+-induced release of gamma-[3H]aminobutyric acid [( 3H]GABA) accumulated by slices of rat substantia nigra. SKF 38393 (D1 agonist) and dopamine (dual D1/D2 agonist) were without effect on [3H]GABA efflux by themselves (1-40 microM), or in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) (0.5 mM), but potentiated evoked release in the presence of forskolin (0.5 microM), an adenylate cyclase activator. These increases in release were prevented by the D1 antagonist SCH 23390 (0.5 microM), but not by the D2 antagonist metoclopramide (0.5 microM). Higher concentrations of forskolin (10-40 microM) augmented stimulus-evoked [3H]GABA release directly, whereas dibutyryl cyclic AMP (100-200 microM) depressed it. Apomorphine, noradrenaline, and 5-hydroxytryptamine (1-40 microM) had no effect. The D2 stimulants lisuride, RU 24213, LY 171555, and bromocriptine dose-dependently inhibited depolarisation-induced but not basal [3H]GABA outflow. These inhibitory responses were not modified by the additional presence of SKF 38393 (10 microM) or SCH 23390 (1 microM), or by injection of 6-hydroxydopamine into the medial forebrain bundle 42 days earlier, but were attenuated by metoclopramide (0.5 microM). Higher amounts (10 microM) of SCH 23390, metoclopramide, or other D2 antagonists (loxapine, haloperidol) reduced evoked GABA release by themselves, probably by nonspecific mechanisms. These results suggest D1 and D2 receptors may have opposing effects on nigral GABA output and could explain the variable effects of mixed D1/D2 dopaminomimetics in earlier release and electrophysiological experiments.

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Interactions between dopamine and γ-aminobutyrate in the substantia nigra: Implications for the striatonigral output hypothesis

Cited by 44 publications

References 48 publications

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Amphetamine-induced release of dendritic dopamine in substantia nigra pars reticulata: D1-mediated behavioral and electrophysiological effects

Opposing Roles of Dopamine D₁ and D₂ Receptors in Nigral γ‐[³H]Aminobutyric Acid Release?

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Interactions between dopamine and γ-aminobutyrate in the substantia nigra: Implications for the striatonigral output hypothesis

Cited by 44 publications

References 48 publications

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Amphetamine-induced release of dendritic dopamine in substantia nigra pars reticulata: D1-mediated behavioral and electrophysiological effects

Opposing Roles of Dopamine D1 and D2 Receptors in Nigral γ‐[3H]Aminobutyric Acid Release?

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Opposing Roles of Dopamine D₁ and D₂ Receptors in Nigral γ‐[³H]Aminobutyric Acid Release?