D-Cycloserine, a positive modulator of NMDA receptors, inhibits serotonergic function

The administration of the N-methyl-D-aspartate (NMDA)-associated glycine re cognition site agonist D-cycloserine (DCS) to rats inhibited the head shake s and the forepaw treading induced by the serotonin (5HT) precursor, L-5-hy droxy-tryptophan [(-)5HTP], as well as the forepaw treading and motility el icited by the selective 5HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propyla mino)tetralin (8-OH-DPAT). The head shakes typically induced by the 5HT(2) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), were unaffected by DCS pretreatment. The results are consistent with reduce d serotonergic transmission produced by NMDA activation, as suggested by ot her authors. Due to the important role played in the pathogenesis of schizo phrenia by glutamate deficiency/serotonin activation, the results support t he view that positive modulators of NMDA receptors, activating glutamate re ceptors and reducing serotonergic tone, might he useful in the alleviation of psychotic symptoms. However, because of its partial agonist properties a t the glycine recognition site, D-cycloserine shows some effects that might make it unsuitable for clinical use. (C) 2000 Lippincott Williams & Wilkin s.