Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain.

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Tordera R, Pei Q, Newson M, Gray K, Sprakes M, Sharp T

Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain.

Neuropharmacology. 2003 Jun;44(7):893-902.

PubMed ID

12726821 [ View in PubMed

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Abstract

Selective 5-HT(1A) receptor antagonists enhance the effect of selective serotonin reuptake inhibitors (SSRIs) on presynaptic 5-HT function, and have potential as antidepressant augmentation therapies. The present study tested the effect of different selective 5-HT(1A) receptor antagonists (WAY 100635, NAD-299, p-MPPI and LY 426965) in combination with a SSRI (paroxetine), on postsynaptic 5-HT function measured by increased expression of the immediate early gene, Arc. Paroxetine (5 mg/kg s.c.) combined with WAY 100635 (0.3 mg/kg s.c.) increased Arc mRNA in frontal, parietal and piriform cortices, and caudate putamen. Paroxetine (5 mg/kg s.c.) plus NAD-299 (1 or 5 mg/kg s.c.) had a similar effect. None of these drugs increased Arc mRNA when administered alone. Paroxetine (5 mg/kg s.c.) plus p-MPPI (8.5 mg/kg s.c.) also increased Arc mRNA but p-MPPI itself elevated Arc mRNA in many regions. Whilst LY 426965 (3 or 10 mg/kg s.c.) had no effect alone, when combined with paroxetine (5 mg/kg s.c.), the drug increased Arc mRNA in caudate putamen but not cortical regions.In conclusion, this study demonstrates that four 5-HT(1A) receptor antagonists augment the effect of an SSRI on Arc mRNA expression, which is suggestive of increased postsynaptic 5-HT function. However, the data reveal certain differences in the 5-HT(1A) receptor antagonists not recognised in models of presynaptic 5-HT function.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Robalzotan	5-hydroxytryptamine receptor 1A	Protein	Humans	Unknown	Not Available	Details