A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to l-DOPA in a rodent model of Parkinson's disease

Tomiyama, Masahiko; Kimura, Takuma; Maeda, Tetsuya; Kannari, Kazuya; Matsunaga, M; Baba, Masayuki

doi:10.1016/j.neures.2005.03.004

Cited by 67 publications

(57 citation statements)

References 42 publications

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“…It also prevented the increase in levels of dynorphin and glutamic acid decarboxylase mRNA in the dopamine-denervated striatum that have again been proposed as markers of dyskinesia induction (Tomiyama et al, 2005). These findings suggest that 5-HT 1a receptors activation may prevent the development of levodopa-induced dyskinesia.…”

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confidence: 56%

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

Iravani

Tayarani-Binazir

Chu

et al. 2006

J Pharmacol Exp Ther

108

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5-Hydroxytryptamine 1a (5-HT 1a ) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopainduced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT 1a receptors and also possess dopamine antagonist actions. We now report on the effects of (2R), a selective 5-HT 1a agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(ϩ)-8-OHDPAT (0.2, 0.6, and 2.0 mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(ϩ)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(ϩ)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(ϩ)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT 1a recep-(1.0 mg/kg s.c.). Administration of (R)-(ϩ)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced by the administration of the D 2 /D 3 dopamine receptor agonist pramipexole (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT 1a agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism.

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confidence: 56%

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

Iravani

Tayarani-Binazir

Chu

et al. 2006

J Pharmacol Exp Ther

108

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“…In DA-depleted striatonigral neurons, L-DOPA and D1R agonists increase dynorphin/PPD, GAD65, and GAD67 gene expression 7,28,32,43,44 and these changes are positively correlated with dyskinesia. 7,28,32 Corroborating previous reports, treatment with SKF81297 on test day induced pronounced dyskinesia ( Figure 2A) and augmented PPD, GAD65, and GAD67 mRNA in the DA-depleted striatum compared to vehicle treatment ( Figure 2C−E).…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

Effects of 5-HT_1A Receptor Stimulation on D1 Receptor Agonist-Induced Striatonigral Activity and Dyskinesia in Hemiparkinsonian Rats

Dupre

Ostock

George

et al. 2013

ACS Chem. Neurosci.

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Accumulating evidence supports the value of 5-HT 1A receptor (5-HT 1A R) agonists for dyskinesias that arise with long-term L-DOPA therapy in Parkinson's disease (PD). Yet, how 5-HT 1A R stimulation directly influences the dyskinetogenic D1 receptor (D1R)-expressing striatonigral pathway remains largely unknown. To directly examine this, one cohort of hemiparkinsonian rats received systemic injections of Vehicle + Vehicle, Vehicle + the D1R agonist SKF81297 (0.8 mg/kg), or the 5-HT 1A R agonist ±8-OH-DPAT (1.0 mg/kg) + SKF81297. Rats were examined for changes in abnormal involuntary movements (AIMs), rotations, striatal preprodynorphin (PPD), and glutamic acid decarboxylase (GAD; 65 and 67) mRNA via RT-PCR. In the second experiment, hemiparkinsonian rats received intrastriatal pretreatments of Vehicle (aCSF), ±8-OH-DPAT (7.5 mM), or ±8-OH-DPAT + the 5-HT 1A R antagonist WAY100635 (4.6 mM), followed by systemic Vehicle or SKF81297 after which AIMs, rotations, and extracellular striatal glutamate and nigral GABA efflux were measured by in vivo microdialysis. Results revealed D1R agonist-induced AIMs were reduced by systemic and intrastriatal 5-HT 1A R stimulation while rotations were enhanced. Although ±8-OH-DPAT did not modify D1R agonist-induced increases in striatal PPD mRNA, the D1R/5-HT 1A R agonist combination enhanced GAD65 and GAD67 mRNA. When applied locally, ±8-OH-DPAT alone diminished striatal glutamate levels while the agonist combination increased nigral GABA efflux. Thus, presynaptic 5-HT 1A R stimulation may attenuate striatal glutamate levels, resulting in diminished D1R-mediated dyskinetic behaviors, but maintain or enhance striatal postsynaptic factors ultimately increasing nigral GABA levels and rotational activity. The current findings offer a novel mechanistic explanation for previous results concerning 5-HT 1A R agonists for the treatment of dyskinesia.

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“…However, inhibition of the expression of the established behavioral sensitization was caused by the 5-HT 3 receptor antagonist, ondansetron, and some agents with the 5-HT 2A receptor antagonist property including clozapine, mianserin, and ketanserin (Davidson et al, 2002a, b). Activation of the 5-HT 1A receptor was reported to prevent the development of the behavioral sensitization to L-DOPA (L-3,4-dihydroxyphenylalanine) (Tomiyama et al, 2005), but has not yet been tested with respect to the established sensitization phenomenon. To clarify the 5-HT receptor subtypes critical for the reversal effects of SSRIs on the expression of the MAP sensitization, further investigation is needed to try to block the reversal effects using 5-HT 1B , 5-HT 2A , 5-HT 1A , 5-HT 2C , and 5-HT 3 antagonists.…”

Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine

Kaneko

Kashiwa

Ito

et al. 2006

Neuropsychopharmacol

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To obtain an insight into the development of a new pharmacotherapy that prevents the treatment-resistant relapse of psychostimulantinduced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors (SSRI), fluoxetine (FLX) and paroxetine (PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) or PRX (8 mg/kg, s.c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis and schizophrenia.

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A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to l-DOPA in a rodent model of Parkinson's disease

Cited by 67 publications

References 42 publications

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

Effects of 5-HT_1A Receptor Stimulation on D1 Receptor Agonist-Induced Striatonigral Activity and Dyskinesia in Hemiparkinsonian Rats

Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine

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A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to l-DOPA in a rodent model of Parkinson's disease

Cited by 67 publications

References 42 publications

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

In 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates, the Selective 5-Hydroxytryptamine 1a Agonist (R)-(+)-8-OHDPAT Inhibits Levodopa-Induced Dyskinesia but Only with\ Increased Motor Disability

Effects of 5-HT1A Receptor Stimulation on D1 Receptor Agonist-Induced Striatonigral Activity and Dyskinesia in Hemiparkinsonian Rats

Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine

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Effects of 5-HT_1A Receptor Stimulation on D1 Receptor Agonist-Induced Striatonigral Activity and Dyskinesia in Hemiparkinsonian Rats