The effects of serotonin (5-HT) and related agonists and antagonists on phosphoinositide turnover have been investigated in several brain regions of the immature rat. In the presence of LiCl, 5-HT caused a marked increase in total [3H]inositol phosphate levels in cortical (maximal effect + 420%, EC50 = 7 microM) and to a lesser extent in hippocampal and striatal slices prepared from the immature (8-day-old) rat; the cortical 5-HT-induced phosphoinositide response was tetrodotoxin resistant. The magnitude of the increase in the cortical phosphoinositide response caused by 5-HT was maximal at 1 day postnatal and progressively declined to reach 6% of this maximal response in the adult. After incubation of immature (8-day-old) rat cortical slices for 2.5 min with 5-HT (in the absence of LiCl), inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate levels increased about 2-fold. A variety of 5-HT2 or mixed 5-HT1/5-HT2 agonists stimulated total [3H]inositol phosphate formation in the immature rat cortex and hippocampus with a rank order of potency [alpha(+)-methyl-5-HT greater than quipazine greater than MK 212 greater than 5-HT] which resembles their potencies at the 5-HT2 binding site. In contrast, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin, the 5-HT1B agonists 1-(m-trifluoromethylphenyl)piperazine and 1-(m-chlorophenyl)-piperazine and the 5-HT3 agonist 2-methyl-5-HT were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)