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Intranigral GR-113808, a Selective 5-HT4 Receptor Antagonist, Attenuates Morphine-Stimulated Dopamine Release in the Rat Striatum

Intranigral GR-113808, a Selective 5-HT4 Receptor Antagonist, Attenuates Morphine-Stimulated Dopamine Release in the Rat Striatum

L Pozzi, L Trabace, R Invernizzi, R Samanin

Brain Res. 1995 Sep 18;692(1-2):265-8.

PMID: 8548313

Abstract:

GR-113808, a potent and selective 5-HT4 receptor antagonist, was infused through a microdialysis probe into the striatum and nucleus accumbens of awake rats, and basal and morphine-stimulated extracellular concentrations of dopamine (DA) were measured in these regions. At 1 and 10 microM GR-113808 did not affect the extracellular concentrations of DA in either region and 100 microM significantly reduced dialysate DA only in the striatum. A subcutaneous dose of 5 mg/kg morphine significantly raised extracellular concentrations of DA in the striatum and nucleus accumbens from 60 to 120 min after injection and the effect was not modified by 10 microM GR-113808 infused through the probe 20 min before and for 60 min after morphine. Bilateral injections of GR-113808 (1, 2.5 and 10 micrograms/0.5 microliter) in the substantia nigra pars compacta did not affect dialysate DA in the striatum, except for a significant increase 120 min after the injection of 10 micrograms but the highest dose of GR-113808 prevented the increase of striatal DA caused by 5 mg/kg morphine s.c. The results suggest that 5-HT4 receptors in the substantia nigra modulate the activity of the dopaminergic nigrostriatal system only when the neurons are activated.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP144625514	GR 113808		144625-51-4	Price

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