Dopamine D1 Receptors Synergize with D2, But Not D3 or D4, Receptors in the Striatum without the Involvement of Action Potentials

LaHoste, Gerald J.; Henry, Brook L.; Marshall, John F.

doi:10.1523/jneurosci.20-17-06666.2000

Cited by 66 publications

(56 citation statements)

References 41 publications

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“…Our observation of a general suppression of FSIs is also consistent with an eticlopride-induced reduction in the number of PV + cells that express c-fos following cortical stimulation (Trevitt et al, 2005). Though supported by such prior evidence, our direct demonstration of firing rate changes is important because dopaminergic mechanisms can affect gene expression through multiple signal transduction pathways, which do not necessarily involve changes in spiking (Berke et al, 1998;LaHoste et al, 2000). Although we observed a bidirectional control of FSI firing rates with dopaminergic drugs, we note that a significant change in FSI firing rate was not observed after the broad removal of dopamine by 6-hydroxydopamine lesion (Mallet et al, 2006).…”

Section: Discussionsupporting

confidence: 83%

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

Wiltschko

Pettibone

Berke

2010

Neuropsychopharmacol

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Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by distinguishing between medium spiny projection neurons (MSNs) and presumed fast-spiking interneurons (FSIs), in freely moving rats. The response of MSNs to both the stimulant amphetamine (0.5 or 2.5 mg/kg) and the antipsychotic eticlopride (0.2 or 1.0 mg/kg) remained highly heterogeneous, with each drug causing both increases and decreases in the firing rate of many MSNs. By contrast, FSIs showed a far more uniform, dose-dependent response to both drugs. All FSIs had decreased firing rate after high eticlopride. After high amphetamine most FSIs increased firing rate, and none decreased. In addition, the activity of the FSI population was positively correlated with locomotor activity, whereas the MSN population showed no consistent response. Our results show a direct relationship between the psychomotor effects of dopaminergic drugs and the firing rate of a specific striatal cell population. Striatal FSIs may have an important role in the behavioral effects of these drugs, and thus may be a valuable target in the development of novel therapies.

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Section: Discussionsupporting

confidence: 83%

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

Wiltschko

Pettibone

Berke

2010

Neuropsychopharmacol

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“…We present data demonstrating that D 1 -like receptor pathways may act in parallel with D 2 -like receptor pathways to increase the stability of a preexisting 5-HT-, NMA-induced rhythm. Evidence in the brain and spinal cord supports the finding that a synergy between D 1 and D 2 receptor-based signaling pathways exists and functions to produce appropriate behavioral output in the brain and spinal cord (Barrière et al 2004;Braun and Chase 1986;LaHoste et al 2000;Missale et al 1998). However, it is important to note that application of the D 1 -like antagonist LE 300 resulted in degradation of the stable 5-HT-, NMA-, dopamine-evoked locomotor-like rhythm, while the D 2 -like antagonist L-741,626 with preferential binding affinity for D 2 only degraded rhythm stability in the presence of the D 2 -like agonist quinpirole, and not when dopamine was present.…”

Section: Discussionmentioning

confidence: 73%

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Sharples

Humphreys

Jensen

et al. 2015

Journal of Neurophysiology

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Sharples SA, Humphreys JM, Jensen AM, Dhoopar S, Delaloye N, Clemens S, Whelan PJ. Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord. J Neurophysiol 113: 2500 -2510, 2015. First published February 4, 2015 doi:10.1152/jn.00849.2014.-Dopamine is now well established as a modulator of locomotor rhythms in a variety of developing and adult vertebrates. However, in mice, while all five dopamine receptor subtypes are present in the spinal cord, it is unclear which receptor subtypes modulate the rhythm. Dopamine receptors can be grouped into two families-the D 1/5 receptor group and the D 2/3/4 group, which have excitatory and inhibitory effects, respectively. Our data suggest that dopamine exerts contrasting dose-dependent modulatory effects via the two receptor families. Our data show that administration of dopamine at concentrations Ͼ35 M slowed and increased the regularity of a locomotor rhythm evoked by bath application of 5-hydroxytryptamine (5-HT) and N-methyl-D(L)-aspartic acid (NMA).This effect was independent of the baseline frequency of the rhythm that was manipulated by altering the NMA concentration. We next examined the contribution of the D 1 -and D 2 -like receptor families on the rhythm. Our data suggest that the D 1 -like receptor contributes to enhancement of the stability of the rhythm. Overall, the D 2 -like family had a pronounced slowing effect on the rhythm; however, quinpirole, the D 2 -like agonist, also enhanced rhythm stability. These data indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal locomotor pattern generator. dopamine; locomotion; monoamine; spinal cord NEURAL CIRCUITS that produce basic rhythmic motor patterns of locomotion, in vertebrates, reside primarily in the spinal cord and are subject to neuromodulation from a wide range of sources both intrinsic and extrinsic to the spinal cord (Dunbar et al.

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“…The expression of D1 and D2 receptors within neurons in brain tissues and cultured neurons was analyzed. D1-like and D2-like receptors have been shown to be co-localized in neurons of the rodent striatum (14); however, there has been some controversy as to whether the D1 and D2 receptor subtypes are co-expressed in the same cell (14,28). Using antibodies that were specific for the D1 and D2 receptors, we substantiated the subtype selectivity and performed immunohistochemical analysis of human and rat brain.…”

Section: Co-activation Of D1 and D2 Receptors Elevates Intracellularmentioning

confidence: 92%

Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal

Lee¹,

So²,

Rashid

et al. 2004

Journal of Biological Chemistry

403

361

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Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist. Calcium signaling by D1-D2 receptor co-activation was abolished following treatment with a phospholipase C inhibitor but not with pertussis toxin or inhibitors of protein kinase A or protein kinase C, indicating coupling to the G q pathway. We also show, by co-immunoprecipitation from rat brain and from cells co-expressing the receptors, that D1 and D2 receptors are part of the same heteromeric protein complex and, by immunohistochemistry, that these receptors are co-expressed and co-localized within neurons of human and rat brain. This demonstration that D1 and D2 receptors have a novel cellular function when co-activated in the same cell represents a significant step toward elucidating the mechanism of the functional link observed between these two receptors in brain.The dopamine D1 receptor has been shown to signal via G s and G olf proteins to stimulate adenylyl cyclase (1), and there have been reports of calcium signaling by D1 receptor-mediated phosphatidylinositol hydrolysis by phospholipase C (PLC), 1 presumably through G q coupling. Although PLC activity was not detected in studies on the D1 receptor expressed in COS7 cells (2) or in Chinese hamster ovary and baby hamster kidney cells (3), it has been shown that activation of the D1 receptor in brain tissue (4, 5) or in Xenopus oocytes injected with mRNA taken from striatum (6) resulted in phosphatidylinositol turnover. This discrepancy suggests the involvement of a factor in D1 receptor-mediated PLC activity that is present in native tissues but absent in heterologous expression systems. An examination of the above studies where PLC activation was observed indicates that, although D1 receptor-selective antagonists blocked phosphatidylinositol turnover demonstrating the involvement of the D1 receptor, the amount of agonist used to elicit the response was greater than 100 M, a concentration at which even selective ligands may bind other receptors. For example, SKF 81297, a highly D1-selective agonist, has a K i for the D1 receptor of ϳ1 nM but has a K i for the D2 receptor of ϳ900 nM (7). This analysis suggests the possibility that the D1 agonistmediated PLC stimulation by high concentrations of drugs observed in physiological systems may have resulted from the coincident activation of another receptor.There are considerable data indicating that the dopamine D1 and D2 receptors are functionally linked. For example, behavioral studies have shown that co-stimulation of the D1 receptor is essential for D2 agonists to produce maximal locomotor stim...

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Dopamine D₁ Receptors Synergize with D₂, But Not D₃ or D₄, Receptors in the Striatum without the Involvement of Action Potentials

Cited by 66 publications

References 41 publications

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal

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