Abstract
The effect of SB-224289 (2,3,6.7-tetrahydro-1'-methyl-5-¿2'-methyl-4'-[(5-methyl-1,2,4-oxadiazol e-3-yl)biphenyl-4-yl]carbonyl¿Furo[2,3-F]-indole-3-spiro-4'-piperidine oxalate) (4 mg/kg i.p., 5-HT1B receptor antagonist), GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide) (0.3 mg/kg i.p., 5-HT1B/1D receptor antagonist), and paroxetine (10 mg/kg p.o.) were investigated on extracellular 5-hydroxytryptamine (5-HT) levels in the frontal cortex, striatum and dentate gyrus of the freely moving guinea-pig with microdialysis. In the frontal cortex and striatum (dorsal raphe innervated areas), GR 127935 evoked a significant decrease in extracellular 5-HT, reaching minima of 41+/-12% and 32+/-6% of basal, respectively. This decrease may be explained by antagonism of inhibitory 5-HT1B/1D receptors on raphe cell bodies, leading to a local increase in 5-HT, which, in turn, stimulated 5-HT1A receptors to decrease cell firing, and hence 5-HT release from terminals. In contrast, SB-224289 had no effect on 5-HT levels in either region. In the dentate gyrus (median raphe innervated area), GR 127935 and SB-224289 significantly increased extracellular 5-HT, reaching m...Continue Reading
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