DIFFERENTIAL REGIONAL ANTAGONISM OF 8-OH-DPAT-INDUCED DECREASE IN SEROTONIN SYNTHESIS BY 2 5-HT1A RECEPTOR ANTAGONISTS

The effects of two 5-HT1A receptor antagonists, 8-fluuro-3,4-dihydro-2 H-1-benzopyran-5-carboxamide hydrogen (2R,3R)-tartrate monohydrate (NA D-299) and methoxyphenyl)-piperazinyl))ethyl)-N-(2-pyridinyl) cyclohex anecarboxamide trihydrochloride (WAY-100635) on the decrease in 5-hydr oxytryptophan (5-HTP) accumulation evoked by ropylamino-8-hydroxy-1,2, 3,1-tetrahydronaphthalene (8-OH-DPAT) in rats treated with the decarbo xylase inhibitor, 3-hydroxyphenylhydrazine (NSD 1015) were studied in four rat brain regions: hippocampus, hypothalamus, striatum and fronta l cortex. Dose-response studies revealed differential effects of both antagonists in the areas examined. Both antagonists were significantly more potent in antagonising the effect of 0.30 and 0.76 mu mol/kg s.c . 8-OH-DPAT in hippocampus than in hypothalamus, striatum and frontal cortex in mentioned order. This order of potency was the opposite to t hat found for 8-OH-DPAT in decreasing the 5-HTP accumulation. Since pr evious studies by others have indicated that the reserve of somatodend ritic 5-HT1A receptors is greater in dorsal raphe nucleus innervating frontal cortex and striatum than in median raphe nucleus which mainly innervates hippocampus, the observed different regional potency of the two 5-HT1A receptor antagonists may be explained by this difference i n the 5-HT1A receptor reserve. (C) 1998 Elsevier Science B.V.