RGD Reference Report - Local modulation of striatal glutamate efflux by serotonin 1A receptor stimulation in dyskinetic, hemiparkinsonian rats. - Rat Genome Database

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Local modulation of striatal glutamate efflux by serotonin 1A receptor stimulation in dyskinetic, hemiparkinsonian rats.

Authors: Dupre, KB  Ostock, CY  Eskow Jaunarajs, KL  Button, T  Savage, LM  Wolf, W  Bishop, C 
Citation: Dupre KB, etal., Exp Neurol. 2011 Jun;229(2):288-99. Epub 2011 Feb 22.
RGD ID: 5683628
Pubmed: PMID:21352823   (View Abstract at PubMed)
PMCID: PMC3100430   (View Article at PubMed Central)
DOI: DOI:10.1016/j.expneurol.2011.02.012   (Journal Full-text)

Serotonin 1A receptor (5-HT(1A)R) agonists reduce both L-DOPA- and D1 receptor (D1R) agonist-mediated dyskinesia, but their anti-dyskinetic mechanism of action is not fully understood. Given that 5-HT(1A)R stimulation reduces glutamatergic neurotransmission in the dopamine-depleted striatum, 5-HT(1A)R agonists may diminish dyskinesia in part through modulation of pro-dyskinetic striatal glutamate levels. To test this, rats with unilateral medial forebrain bundle dopamine or sham lesions were primed with L-DOPA (12 mg/kg+benserazide, 15 mg/kg, sc) or the D1R agonist SKF81297 (0.8 mg/kg, sc) until abnormal involuntary movements (AIMs) stabilized. On subsequent test days, rats were treated with vehicle or the 5-HT(1A)R agonist +/-8-OH-DPAT (1.0 mg/kg, sc), followed by L-DOPA or SKF81297, or intrastriatal +/-8-OH-DPAT (7.5 or 15 mM), followed by L-DOPA. In some cases, the 5-HT(1A)R antagonist WAY100635 was employed to determine receptor-specific effects. In vivo microdialysis was used to collect striatal samples for analysis of extracellular glutamate levels during AIMs assessment. Systemic and striatal +/-8-OH-DPAT attenuated L-DOPA-induced dyskinesia and striatal glutamate efflux while WAY100635 reversed +/-8-OH-DPAT's effects. Interestingly, systemic +/-8-OH-DPAT diminished D1R-mediated AIMs without affecting glutamate. These findings indicate a novel anti-dyskinetic mechanism of action for 5-HT(1A)R agonists with implications for the improved treatment of Parkinson's disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR1AHumanDrug-Induced Dyskinesia  ISOHtr1a (Rattus norvegicus) RGD 
Htr1aRatDrug-Induced Dyskinesia  IMP  RGD 
Htr1aMouseDrug-Induced Dyskinesia  ISOHtr1a (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr1a  (5-hydroxytryptamine receptor 1A)

Genes (Mus musculus)
Htr1a  (5-hydroxytryptamine (serotonin) receptor 1A)

Genes (Homo sapiens)
HTR1A  (5-hydroxytryptamine receptor 1A)


Additional Information