In vivo determination of 5-hydroxytryptamine receptor-stimulated phosphoinositide turnover in rat brain.

In the intact rat brain, phosphoinositide turnover is stimulated by activation of the 5-HT2 receptor. After prelabeling brain phosphoinositides with [3H]inositol, lithium treatment increased levels of [3H]IP1 and [3H]IP2. The 5-HT agonists 5-MeODMT and quipazine further increased 3H-inositol phosphate levels under lithium pretreatment. This response was blocked by the 5-HT2 antagonist ritanserin but not by the 5-HT1 antagonist (-)-propranolol, indicating that 5-HT2 receptors drive this signaling. The method can be used to study in vivo effects of psychotropic drugs like antidepressants on 5-HT2 receptor-stimulated phosphoinositide turnover.

Study at a glance

Abstract

Phosphoinositide turnover stimulated by 5-hydroxytryptamine (5-HT) receptors in the intact rat brain was studied using an in vivo method. Phosphoinositides in the rat brain were prelabeled with [3H]inositol injected into the lateral cerebral ventricles. The rats were killed by microwave irradiation after 48 h and the contents in the frontal cortex of 3H-inositol phosphates, [3H]inositol-1-monophosphate [( 3H]IP1), [3H]inositol-1,4-bisphosphate [( 3H]IP2), and a mixture of [3H]inositol-1,4,5-trisphosphate and [3H]inositol-1,3,4-trisphosphate [( 3H]IP3) were assayed by HPLC. Lithium treatment (10 mEq/kg, i.p., 2 h before) increased the content of [3H]IP1 and [3H]IP2. 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) and quipazine, 5-HT agonists, significantly increased the amount of 3H-inositol phosphates under lithium pretreatment. The response to 5-MeODMT was inhibited by ritanserin, a 5-HT2 antagonist, but not by (-)-propranolol, a 5-HT1 antagonist. These results suggest that phosphoinositide turnover in the rat frontal cortex in vivo is stimulated by 5-HT2 receptor activation. It is considered that this method will be useful for measurement of 5-HT2 receptor-stimulated phosphoinositide turnover in vivo to examine the in vivo effects of various psychotropic drugs such as antidepressants.