Stimulation by neurotensin of (3H)5-hydroxytryptamine (5HT) release from rat frontal cortex slices

Abstract The effect of neurotensin (NT) on the K + -evoked ( 3 H)5HT release from brain frontal cortex slices was studied in rats. NT(1–13) and NT(8–13) increased ( 3 H)5HT release with EC 50 values in the nanomolar range and Emax values in the range of 100% of control, whereas D-tyr 11 -NT was inactive. Concerning NT receptor antagonists, SR 48692 and SR 142948A antagonized with IC 50 values of 4.8 ± 1.8 nM and 4.5 ± 1.8 nM respectively, the NT stimulated K + -evoked ( 3 H)5HT release. SR 48527 also antagonized NT induced ( 3 H)5HT release with an IC 50 value of 0.95 ± 0.06 nM whereas the inactive R(−) enantiomer SR 49711 only inhibited this effect with IC 50 value close to 10 −6 M. The 5HT-releasing effect of NT was completely inhibited by tetrodotoxin suggesting that NT receptors involved in the control of 5-HT release are not located on 5-HT terminals. After a first NT (10 −7 M) application, the NT (10 −7 M, 10 −6 M) effect under K + depolarization was drastically decreased, indicating that the NT receptor could be desensitized. No potentiating effect of NT on K + -evoked ( 3 H)5HT release was observed in striatal and hippocampal slices. These results suggest that, in the rat frontal cortex, NT regulates 5HT release through a high affinity NT receptor not associated with 5HT terminals.