Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain

Araki, Tsutomu; Tanji, Haruko; Kato, Harubumi; Imai, Yutaka; Mizugaki, Michinao; Itoyama, Yasuto

doi:10.1016/s0924-977x(00)00094-8

Cited by 16 publications

(8 citation statements)

References 59 publications

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“…By contrast to our observations for D 1 R, STN‐HFS induced a large decrease in D 2 R and D 3 R levels in the NAcc, regardless of the dopaminergic state of the animals, enhancing the effects of the dopaminergic lesion for D 2 R. It may appear surprising that striatal D 2 R levels remained unchanged in our lesioned animals, whereas increases have frequently been reported after the lesioning of DA neurons of the SNc . However, more detailed studies on PD patients and PD animal models have revealed that the level of DAergic denervation is a key factor influencing the expression of striatal D 2 R .…”

Section: Discussioncontrasting

confidence: 99%

“…In the medial part of the ST, it resulted in D 1 R levels higher than those of nonstimulated animals for both control and 6‐OHDA–lesioned animals. Despite the lack of a general consensus concerning the changes in D 1 R expression occurring in PD patients or in animal models of the disease, we can hypothesize that the decrease in the number of D 1 R sites reported by several autoradiographic studies with [ 3 H]SCH23390 and observed here in the lateral part of the ST of our lesioned rats may contribute to the expression of PD motor symptoms. Indeed, in physiological conditions, DA facilitates movement by activating the striatal‐projecting neurons of the BG direct pathway, most of which bear D 1 R .…”

Section: Discussionmentioning

confidence: 52%

“…50,51 By contrast to our observations for D 1 R, STN-HFS induced a large decrease in D 2 R and D 3 R levels in the NAcc, regardless of the dopaminergic state of the animals, enhancing the effects of the dopaminergic lesion for D 2 R. It may appear surprising that striatal D 2 R levels remained unchanged in our lesioned animals, whereas increases have frequently been reported after the lesioning of DA neurons of the SNc. 34,52,53 However, more detailed studies on PD patients and PD animal models have revealed that the level of DAergic denervation is a key factor influencing the expression of striatal D 2 R. [54][55][56] Thus, changes in striatal postsynaptic receptor density occur only after the almost complete destruction (>90%) of the nigrostriatal DAergic pathway. These findings may account for the lack of significant change in striatal D 2 R density observed in our study and reported elsewhere, 57-59 because 72.6 6 6.07% of the DAergic neurons of the SNc were lost in our 6-OHDA group.…”

Section: S T R I a T A L D A R E C E P T O R E X P R E S S I O N A F mentioning

confidence: 99%

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Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

et al. 2015

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High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h) unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT to assess the densities of D1R, D2R, and D3R, respectively, within different areas of the striatum-a major input structure of the basal ganglia-including the nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN-HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN-HFS on striatal D1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 52%

Section: S T R I a T A L D A R E C E P T O R E X P R E S S I O N A F mentioning

confidence: 99%

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Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

et al. 2015

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“…These observations are consistent with our present findings. Furthermore, consistent with the present findings, Araki et al also observed that the upregulation in D 2 receptors was more pronounced than that in D 1 receptors in the striatum after 6-OHDA lesioning [21,22].…”

Section: Discussionsupporting

confidence: 93%

Changes in Dopamine D2 Receptors and 6-[18F]Fluoro-L-3,4-Dihydroxyphenylalanine Uptake in the Brain of 6-Hydroxydopamine- Lesioned Rats

et al. 2004

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We studied tracer distributions in positron emission tomography of ligands for dopamine D₁ receptors ([¹¹C]SCH23390) and D₂ receptors ([¹¹C]raclopride) and the dopamine precursor analog 6-[¹⁸F]fluoro-L-3,4-dihydroxyphenylalanine ([¹⁸F]FDOPA), as a measurement of presynaptic dopaminergic function, in the brain after 6-hydroxydopamine lesioning of the medial forebrain bundle in rats. The unilateral lesions were confirmed behaviorally by methamphetamine-induced rotation 2 weeks after lesioning, and the brains were analyzed by tissue dissection following an intravenous bolus of each tracer 3 weeks after lesioning. [¹¹C]Raclopride, but not [¹¹C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side. On the other hand, a lower accumulation of [¹⁸F]FDOPA was found in the striatum and cerebral cortex on the lesion side. Our studies demonstrate upregulation of dopamine D₂ receptors in the striatum and a decrease in FDOPA uptake in both the striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions. Therefore, the combination of a D₂ antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson’s disease.

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“…This suggests that rather than diminish corticostriatal glutamatergic innervation, dopamine depletion is associated with an increase in the strength of this pathway under baseline conditions. Other explanations for the blockade of synaptic plasticity after dopamine depletion of the striatum include changes in glutamate receptor density or subtype, which also occur in the 6-OHDA lesion model of PD (55)(56)(57)(58). Additional experiments are needed to determine the precise mechanism through which degeneration of the dopaminergic nigrostriatal pathway alters glutamate signaling so as to preclude striatal synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

MPTP‐induced deficits in striatal synaptic plasticity are prevented by glial cell line‐derived neurotrophic factor expressed via an adeno‐associated viral vector

Chen

Harvey²,

Hoffman³

et al. 2007

FASEB j.

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This study determined the consequences of dopamine denervation of the striatum on synaptic plasticity and prevention of these changes with gene therapy using an adeno-associated viral vector (AAV) expressing glial cell line-derived neurotrophic factor (GDNF). C57BL6/J mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP); long-term depression (LTD) or potentiation (LTP) were measured in vitro. Fast-scan cyclic voltammetry measured electrically released dopamine from a functionally relevant pool in these same striatal slices. After MPTP, dopamine release and uptake were greatly diminished, and LTP and LTD were blocked in the striatal slices. The loss of plasticity resulted directly from the loss of dopamine since its application rescued synaptic plasticity. Striatal GDNF expression via AAV, before MPTP, significantly protected against the loss of dopamine and prevented the blockade of corticostriatal LTP. These data demonstrate that dopamine plays a role in supporting several forms of striatal plasticity and that GDNF expression via AAV prevents the loss of dopamine and striatal plasticity caused by MPTP. We propose that impairment of striatal plasticity after dopamine denervation plays a role in the symptomology of Parkinson's disease and that AAV expression of neurotrophic factors represents a tenable approach to protecting against or slowing these neurobiological deficits.

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Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain

Cited by 16 publications

References 59 publications

Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

Changes in Dopamine D<sub>2</sub> Receptors and 6-[<sup>18</sup>F]Fluoro-<i>L</i>-3,4-Dihydroxyphenylalanine Uptake in the Brain of 6-Hydroxydopamine- Lesioned Rats

MPTP‐induced deficits in striatal synaptic plasticity are prevented by glial cell line‐derived neurotrophic factor expressed via an adeno‐associated viral vector

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