MK-801 reverses effects of chronic levodopa on D1 and D2 dopamine agonist-induced rotational behavior

Boldry, Robert C.; Papa, Stella M.; Kask, Anne M.; Chase, Thomas N.

doi:10.1016/0006-8993(95)00690-r

Cited by 20 publications

(10 citation statements)

References 24 publications

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“…Thus the concomitant reversal of pausing changes in those neurons could be interpreted as pausing participating in the mechanisms of dyskinesias. The release of involuntary movements has been attributed to imbalance of the striatal outputs, as occurring between the direct and indirect pathways (Calabresi et al 2010;Jenner 2008; or among single MSN discharges (Boldry et al 1995;Liang et al 2008). Pauses increased with levodopa influx in the on state, suggesting that pausing may be a constitutive MSN activity pattern in normal motor behavior, but its reversal to the reduced pausing rate of the off state in some MSNs (precisely the same neurons that do not maintain the DA-induced frequency changes) could create an imbalance of discharges and contribute to the expression of dyskinesias.…”

Section: Discussionmentioning

confidence: 99%

Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

Singh

Liang

Kaneoke

et al. 2015

Journal of Neurophysiology

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Section: Discussionmentioning

confidence: 99%

Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

Singh

Liang

Kaneoke

et al. 2015

Journal of Neurophysiology

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“…The efficacy of the dopaminergic lesion was tested by measuring contralateral turning behavior with an acute subthreshold dose of apomorphine (0.05 mg/kg s.c.) 2 weeks post-surgery. Only rats exhibiting more than 200 turns contralateral to the lesion side in 30 min were considered to be compatible with the model of full lesion, and were chosen for further study (Boldry et al, 1995). TH staining revealed also a complete lesion of substantia nigra (SN) ipsilateral to the lesion (see Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats

et al. 2017

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L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined. Rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received daily L-DOPA treatment for 3 weeks, and abnormal involuntary movements (AIMs) were assessed every other day. PD98059 was injected in the lateral ventricle daily for 12 days starting from day 10 of L-DOPA treatment. Striatal molecular markers of LID were analyzed together with gene regulation using microarray. The administration of PD98059 significantly reduced AIMs. In addition, ERK activation and other associated molecular changes including ΔFosB were reversed in rats treated with the MEK inhibitor. PD98059 induced significant up-regulation of 418 transcripts and down-regulation of 378 transcripts in the striatum. Tyrosine hydroxylase (Th) and aryl hydrocarbon receptor nuclear translocator (Arnt) genes were down-regulated in lesioned animals and up-regulated in L-DOPA-treated animals. Analysis of protein levels showed that PD98059 reduced the striatal TH. These results support the association of p-ERK1/2, ΔFosB, p-H3 to the regulation of TH and ARNT in the mechanisms of LID, and pinpoint other gene regulatory changes, thus providing clues for identifying new targets for LID therapy.

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“…Like SKF 81297 and SKF 82958, A-77636 elicits contralateral turning behavior in rats with unilateral lesions (Asin and Wirtshafter 1993;Boldry et al 1995;Ruskin et al 1999). In addition, A-77636 and SKF 82958 show similar efficacy in eliciting turning behavior in monkeys with unilateral MPTP lesions (Domino and Sheng 1993).…”

Section: Introductionmentioning

confidence: 99%

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

Chausmer

Katz

2001

Psychopharmacology

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Rationale: Recent data suggest that dopamine (DA) D 1 -like receptor full agonists may be potential pharmacotherapeutic agents for treating cocaine abuse. The structurally novel isochroman D 1 -like agonist, A-77636, has not been well characterized and may prove to be useful as such an agent. Objectives: The interactions of cocaine and A-77636 were compared to those obtained with the better investigated benzazepine D 1 -like dopamine agonists, SKF 82958 and SKF 81297. The alterations in the locomotor stimulant and discriminativestimulus effects of cocaine by the full D 1 -like dopamine receptor agonists were investigated across a full range of doses in order to characterize their interactions. Methods: Drug-naive Swiss-Webster mice were pretreated with SKF 81297, SKF 82958 or A-77636 (1-10 mg/kg) and cocaine (5-56 mg/kg) prior to a 30-min period in which locomotor activity was assessed. Rats were trained on a fixed ratio 20 (FR20) schedule to discriminate IP saline from cocaine (10 mg/kg) injections. Cocaine alone (1-10 mg/kg) and with either A-77636 (0.56-1.7 mg/kg), SKF 82958 (0.01-0.1 mg/kg) or SKF 81297 (0.1-0.56) were injected IP 5 min prior to a 15-min test session. Results: Cocaine maximally stimulated activity at 20-40 mg/kg with higher and lower doses stimulating activity less. Each D 1 -like agonist produced a dose-related decrease in cocaine-induced locomotor activity and lowered its maximal rate. Each of the D 1 -like agonists partially substituted for cocaine, with maximal substitution approximating 49, 35, and 24% for SKF 81297, SKF 82958, and A-77636, respectively. SKF 82958 significantly shifted the cocaine dose-effect curve approximately 3-fold to the left. With SKF 81297, there was a trend towards a leftward shift of cocaine dose effects, however the change was not statistically significant. In contrast to the other two D 1 -like agonists, A-77636 either did not affect the cocaine dose-effect curve or shifted it to the right. Conclusions: All three agonists produced similar effects on cocaine-induced locomotor activity, however the discriminative-stimulus effects of cocaine were affected differently by the D 1 agonists. These results suggest fundamental differences in the actions of these D 1 agonists. Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse.

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MK-801 reverses effects of chronic levodopa on D1 and D2 dopamine agonist-induced rotational behavior

Cited by 20 publications

References 24 publications

Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

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