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

Starr, Michael S.

doi:10.1111/j.1471-4159.1987.tb09992.x

Cited by 92 publications

(37 citation statements)

References 50 publications

(57 reference statements)

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“…L-DOPA could stimulate D 1 receptors on striatonigral neurons (Gerfen et al, 1990), so to activate the "direct" pathway (Robertson and Robertson, 1989;Carta et al, 2005), or D 1 receptors on striatonigral nerve terminals (Starr, 1987;Aceves et al, 1991). The fact that TTX prevented the L-DOPA effect rules out this latter hypothesis, although it does not exclude an intranigral action of L-DOPA because this agent could stimulate GABAergic interneurons [dendritic location of D 1 receptors has been detected in the SNr (Huang et al, 1992)].…”

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

confidence: 89%

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 Interamentioning

confidence: 89%

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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“…The increase in GABA release by D1 receptor stimulation in the VTA or substantia nigra (Starr, 1987;Timmerman et al, 1991;Cameron and Williams, 1994;Kalivas and Duffy, 1995) is blunted in rats pretreated with repeated injections of cocaine (Bonci and Williams, 1996). This poses the possibility that a D1-mediated reduction in inhibitory GABAergic tone may disinhibit glutamate release.…”

Section: Discussionmentioning

confidence: 99%

Repeated Cocaine Administration Alters Extracellular Glutamate in the Ventral Tegmental Area

Kalivas

Duffy

1998

Journal of Neurochemistry

173

116

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Abstract:The present study determined if repeated cocaine injections alter the effect of cocaine on extracellular glutamate in the ventral tegmental area (VTA). All rats were treated with daily cocaine (15 mg/kg i.p. x 2 days, 30 mg/kg i.p. x 5 days) or saline for 7 days. At 21 days after discontinuing the daily injections, a dialysis probe was placed into the VTA and the extracellular levels of glutamate were estimated. A systemic injection of cocaine (15 mg/kg i.p.) elevated extracellular glutamate in the VTA of rats pretreated with daily cocaine but not in the daily saline-pretreated subjects. No significant change in glutamate was produced by a saline injection in either pretreatment group. In a group of rats pretreated with daily cocaine, the D 1 antagonist SCH-23390 (30 /2M) was infused through the dialysis probe prior to the acute injections of saline and cocaine. SCH-23390 prevented the increase in extracellular glutamate associated with the acute administration of cocaine. Behavioral data were collected simultaneously with the measures of extracelluar glutamate. The behavioral stimulant effect of cocaine was greater in cocaine-pretreated than saline-pretreated subjects, and the behavioral augmentation in cocainepretreated rats was partly blocked by SCH-23390. These data support the hypotheses that repeated cocaine administration produces an increase in the capacity of D1 receptor stimulation to release glutamate in the VTA and that this mechanism partly mediates behavioral sensitization produced in rats treated with daily cocaine injections.

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“…Previous studies in rodents have suggested that D1LR antagonists may increase GABA levels in the SNr under some circumstances (Garcia et al 1997;Starr 1987), although this has not always been seen (Mayfield et al 1999). In our experiments, exposure to the D1LR antagonist increased the electrophysiologic activity of the majority of GPi cells and of a subset of SNr cells.…”

Section: D1lr Antagonist Effectsmentioning

confidence: 99%

“…Dopamine was shown to increase GABA release from rat brain slices in early studies (Reubi et al 1977), or to induce biphasic effects (van der Heyden et al 1980), perhaps explained by the fact that D1LR and D2LR receptors are activated by dopamine. Other studies of GABA release from brain slices showed that D1LR activation potentiates evoked GABA efflux in the SNr (Aceves et al 1995;Floran et al 1990;Starr 1987), although this was not true in other studies (Mayfield et al 1999). Published reports on the effects of D1LR activation on GABA release in vivo, studied in awake rats with microdialysis techniques, have consistently demonstrated that D1LR activation increases GABA levels in the SNr (Matuszewich and Yamamoto 1999;Rosales et al 1997;Timmerman and Westerink 1995;Trevitt et al 2002;You et al 1994) and entopeduncular nucleus (the rodent homologue of the primate GPi; Ferre et al 1996).…”

Section: D1lr Agonist Effectsmentioning

confidence: 99%

Activation of Nigral and Pallidal Dopamine D1-Like Receptors Modulates Basal Ganglia Outflow in Monkeys

Kliem¹,

Maidment²,

Ackerson³

et al. 2007

Journal of Neurophysiology

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Kliem MA, Maidment NT, Ackerson LC, Chen S, Smith Y, Wichmann T. Activation of nigral and pallidal dopamine D1-like receptors modulates basal ganglia outflow in monkeys. J Neurophysiol 98: 1489-1500, 2007. First published July 18, 2007; doi:10.1152/jn.00171.2007. Studies of the effects of dopamine in the basal ganglia have focused on the striatum, whereas the functions of dopamine released in the internal pallidal segment (GPi) or in the substantia nigra pars reticulata (SNr) have received less attention. Anatomic and biochemical investigations have demonstrated the presence of dopamine D1-like receptors (D1LRs) in GPi and SNr, which are primarily located on axons and axon terminals of the GABAergic striatopallidal and striatonigral afferents. Our experiments assessed the effects of D1LR ligands in GPi and SNr on local ␥-aminobutyric acid (GABA) levels and neuronal activity in these nuclei in rhesus monkeys. Microinjections of the D1LR receptor agonist SKF82958 into GPi and SNr significantly reduced discharge rates in GPi and SNr, whereas injections of the D1LR antagonist SCH23390 increased firing in the majority of GPi neurons. D1LR activation also increased bursting and oscillations in neuronal discharge in the 3-to 15-Hz band in both structures, whereas D1LR blockade had the opposite effects in GPi. Microdialysis measurements of GABA concentrations in GPi and SNr showed that the D1LR agonist increased the level of the transmitter. Both findings are compatible with the hypothesis that D1LR activation leads to GABA release from striatopallidal or striatonigral afferents, which may secondarily reduce firing of basal ganglia output neurons. The antagonist experiments suggest that a dopaminergic "tone" exists in GPi. Our results support the finding that D1LR activation may have powerful effects on GPi and SNr neurons and may mediate some of the effects of dopamine replacement therapies in Parkinson's disease.

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

Cited by 92 publications

References 50 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

Repeated Cocaine Administration Alters Extracellular Glutamate in the Ventral Tegmental Area

Activation of Nigral and Pallidal Dopamine D1-Like Receptors Modulates Basal Ganglia Outflow in Monkeys

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