Effects of muscimol and picrotoxin on single unit activity of substantia nigra neurons

Waszczak, Barbara L.; Eng, Nancy; Walters, Judith R.

doi:10.1016/0006-8993(80)90567-3

Cited by 163 publications

(45 citation statements)

References 33 publications

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“…TTX perfusion in the SNr produced per se a rapid decline in VMTh GABA release. This indicates that spontaneous VMTh GABA release partly reflects impulse-dependent neuronal activity and is consistent with the fact that nigrothalamic GABA neurons provide a tonic input to the thalamus (Guyenet and Aghajanian 1978; Waszczak et al, 1980). This input is enhanced after DA lesion (Burbaud et al, 1995), which may explain why GABA levels were higher in the VMTh ipsilateral to the lesioned side.…”

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

confidence: 75%

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: 75%

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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“…1978: Waszczak et al. 19801 and(2) the distinguishing elect~ophysiological features of pars reticulataneurons, including their smooth, sharp, biphasic action potentials of 0.5-0.7 msec duration and their firing rates (typically 10-40 spikes/set), as previously described (Guyenet and Aghajanian, 1978;Waszczak et al, 1980). Verification of correct placement of the electrode tip in the pars reticulata could be made histologically after recording experiments, as detailed below.…”

Section: Methodsmentioning

confidence: 94%

“…Body temperature was maintained at 36-38°C. The techniques for extracellular, single-unit recording and microiontophoresis were the same as described previously (Waszczak and Walters, 1983;Waszczak et al. 1980).…”

Section: Methodsmentioning

confidence: 99%

Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation

Waszczak¹,

Walters²

1986

J. Neurosci.

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Previous reports from this laboratory have described an ability of iontophoretically applied dopamine to attenuate the inhibitory effects of iontophoresed GABA on neurons of the substantia nigra pars reticulata. This finding raised the question of whether endogenous dopamine, released from dendrites of neighboring pars compacta dopamine neurons, might act as a neuromodulator which diminishes the inhibition of pars reticulata neurons evoked by either GABA iontophoresis or electrical stimulation of the striatonigral GABAergic pathway. Extracellular, single-unit activity of pars reticulata neurons was recorded in male rats anesthetized with chloral hydrate. In one set of studies, d-amphetamine, a drug reported to release dopamine from nigral dendrites, was administered intravenously (1.6 mg/kg) during regular, intermittent iontophoretic pulses of GABA. As had been previously observed with iontophoresed dopamine, i.v. amphetamine significantly lessened the inhibition of reticulata neurons produced by GABA application. This change was reflected by a decrease in GABA's inhibitory potency by 22% relative to the control level of inhibition achieved prior to amphetamine administration. Amphetamine caused no decreases in GABA's effectiveness, however, in animals that had previously received treatments that depleted or destroyed nigral dopamine stores, i.e., in rats pretreated with reserpine and alpha- methyl-p-tyrosine, or in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway. In a second set of experiments, amphetamine or dopamine was delivered iontophoretically while monitoring the GABA-mediated (bicuculline-reversible) inhibition of reticulata neurons that can be elicited by striatal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…We hypothesized that the opposite effects of electrical and chemical stimulation could be attributed to differences in the sensitivity of nigrostriatal dopaminergic neurons and GABAergic pars reticulata neurons to GABA. Several studies imply that GABAergic pars reticulata neurons are more sensitive to exogenously applied GABA and/or GABA A agonists (e.g., Grace and Bunney, 1979;Waszczak et al, 1980Waszczak et al, , 1981 or to synaptically released GABA than are the dopaminergic neurons (Grace and Bunney, 1985;Celada et al, 1999). This effect is so robust that the systemic administration of the GABA A agonist, muscimol leads to an increase in the spontaneous firing rate of dopaminergic neurons (Walters and Lakoski, 1978;Grace and Bunney, 1979;Grace et al, 1980) and elicits an increase in striatal dopamine levels (Martin and Haubrich, 1978;Santiago and Westerink, 1992), despite its expected inhibitory effects on dopaminergic neuron firing.…”

Section: Gabaergic Inputs From the Pars Reticulatamentioning

confidence: 99%

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

2004

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Effects of muscimol and picrotoxin on single unit activity of substantia nigra neurons

Cited by 163 publications

References 33 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

Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

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