Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET and microdialysis

Walker, Matthew; Dinelle, Katherine; Kornelsen, Rick; Lee, Anna F.; Farrer, Matthew J.; Stoessl, A. Jon; Sossi, Vesna

doi:10.1186/2191-219x-3-69

Cited by 20 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This seems unlikely as dopaminergic signaling abnormalities were restricted to the striatum and not present in neocortex (Weinshenker et al, 2002b;Schank et al, 2006). Nevertheless, a NE replacement study, though experimentally challenging, would help rule out the possibility that dopamine is responsible for the effect we observed.…”

Section: Discussionmentioning

confidence: 99%

“…One possible reason for this discrepancy is these studies' use of neurotoxins, particularly 6-hydroxydopamine (6-OHDA), to destroy noradrenergic neurons. 6-OHDA is somewhat nonspecific, as it kills dopaminergic (Uretsky and Iversen, 1970;Walker et al, 2013) as well as noradrenergic neurons, and acutely compromises cholinergic signaling (Bear and Singer, 1986). Further, depending on the route of administration and dosage, 6-OHDA lesions may not include all noradrenergic projections in the area of interest.…”

Section: Discussionmentioning

confidence: 99%

“…Once born, Dbh Ϫ/Ϫ mice do not require L-DOPS for survival despite complete NE deficiency. Furthermore, other than lacking NE, their noradrenergic system is largely comparable to NE-competent controls (Weinshenker et al, 2002a;Jin et al, 2004). Dbh ϩ/Ϫ littermates, which are heterozygous for the dopamine ␤-hydroxylase gene and have NE levels comparable to wild-type (Dbh ϩ/ϩ ) mice (Thomas et al, 1998;Bourdélat-Parks et al, 2005;Sanders et al, 2006), were used as controls.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Norepinephrine Is Necessary for Experience-Dependent Plasticity in the Developing Mouse Auditory Cortex

Shepard¹,

Liles

Liu³

2015

J. Neurosci.

View full text Add to dashboard Cite

Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine ␤-hydroxylase knock-out (Dbh Ϫ/Ϫ ) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh Ϫ/Ϫ mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Norepinephrine Is Necessary for Experience-Dependent Plasticity in the Developing Mouse Auditory Cortex

Shepard¹,

Liles

Liu³

2015

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Hence, the moderation of L-DOPA effects by WMC seems to follow a U-shape relation with no effect on MB control in low DA individuals and enhancement MB control in high baseline DA individuals. To our knowledge, only one animal study has directly investigated the relationship between L-DOPA metabolism measured with 18 F-DOPA PET and DA changes with L-DOPA and found that increases in DA metabolites elicited by L-DOPA is greater when DA synthesis capacity is higher [22]. Thus, individuals with higher DA synthesis capacity may produce more DA from L-DOPA, thereby enhancing MB control as observed previously in higher-WMC individuals [11].…”

Section: Introductionmentioning

confidence: 81%

Individual differences in dopamine function underlying the balance between model-based and model-free control

Lee

Deserno

Kroemer

et al. 2019

Preprint

View full text Add to dashboard Cite

Reinforcement learning involves a balance between model-free (MF) and model-based (MB) systems. Recent studies suggest that individuals with either pharmacologically enhanced levels of dopamine (DA) or higher baseline levels of DA exhibit more MB control. However, it remains unknown whether such pharmacological effects depend on baseline DA.Here, we investigated whether effects of L-DOPA on the balance of MB/MF control depend on ventral striatal baseline DA. Sixty participants had two functional magnetic resonance imaging (fMRI) scans while performing a two-stage sequential decision-making task under 150 mg L-DOPA or placebo (counterbalanced), followed by a 4-hour 18 F-DOPA positron emission tomography (PET) scan (on a separate occasion).We found an interaction between baseline DA levels and L-DOPA induced changes in MB control. Individuals with higher baseline DA levels showed a greater L-DOPA induced enhancement in MB control. Surprisingly, we found a corresponding drug-by-baseline DA interaction on MF, but not MB learning signals in the ventromedial prefrontal cortex. We did not find a significant interaction between baseline DA levels and L-DOPA effects on MF control or MB/MF balance.In sum, our findings point to a baseline dependency of L-DOPA effects on differential aspects of MB and MF control. Individual differences in DA washout may be an important moderator of L-DOPA effects. Overall, our findings complement the general notion where higher DA levels is related to a greater reliance on MB control. Although the relationship between phasic DA firing and MF learning is conventionally assumed in the animal literature, the relationship between DA and MF control is not as straightforward and requires further clarification.

show abstract

“…6-OHDA-induced lesioning of dopamine neurons in rats is a widely used model of PD (Simola et al, 2007). Several studies demonstrated differences in IEG induction following administration of a D1like receptor agonist and the contents of dopamine and its metabolites between the lesioned and nonlesioned hemispheres in animals with unilateral 6-OHDA lesions, particularly in the striatum (Berke et al, 1998;Perese et al, 1989;Walker et al, 2013), and in the level of monoamine neurotransmitters in the substantia nigra, hippocampus and frontal cortex (Kamińska et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

Radlicka

Kamińska

Borczyk

et al. 2020

Preprint

View full text Add to dashboard Cite

The development of Parkinson's disease (PD) causes dysfunction of the frontal cortex, which contributes to hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-DOPA alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. In this study, we investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed an RNA-seq analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesion that were treated with L-3,4-dihydroxyphenylalanine (L-DOPA) , for 2 weeks.We used analysis of variance to identify differentially expressed genes and found 48 genes with significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of 5 modules consisting of genes with similar expression patterns. The analyses led to three primary observations. First, the changes in gene expression induced by L-DOPA were bilateral, although only one hemisphere was lesioned. Second, the changes were not restricted to neurons but also appeared to emerge in immune or endothelial cells. Finally, comparisons with databases of drug-induced gene expression signatures revealed multiple nonspecific effects, which indicates that a part of the observed response is a common pattern activated by multiple types of pharmaceuticals in different target tissues.Taken together, our results identify cellular mechanisms in the frontal cortex that are involved in the response to L-DOPA treatment.

show abstract

Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET and microdialysis

Cited by 20 publications

References 39 publications

Norepinephrine Is Necessary for Experience-Dependent Plasticity in the Developing Mouse Auditory Cortex

Norepinephrine Is Necessary for Experience-Dependent Plasticity in the Developing Mouse Auditory Cortex

Individual differences in dopamine function underlying the balance between model-based and model-free control

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

Contact Info

Product

Resources

About