Stress-induced activation of median raphe serotonergic neurons in rats is potentiated by the neurotensin antagonist, SR 48692.

The activation of rostrally projecting serotonergic (5-HT) neurons by acute sound stress is blocked by exogenous administration of the tridecapeptide neurotensin (NT). 5-HT neurons respond to acute sound stress within the median raphe nucleus (MRN), but not within the dorsal raphe nucleus or hindbrain regions. By use of the NT antagonist, SR 48692, the present study examines the involvement of endogenous NT in modulating the preferential activation of MRN 5-HT neurons by sound stress, and extends the findings with sound stress to two other stressors (swim and tail shock). Activation is determined from the enhanced accumulation of 5-hydroxytryptophan (5-HTP) from various brain regions over basal after inhibition of aromatic amino acid decarboxylase. The NT antagonist, SR 48692, enhances the stress activation of MRN 5-HT neurons and its projections without changing 5-HTP accumulation under basal conditions. Thus, the antagonist, SR 48692, unmasks the action of endogenous NT-containing neurons indicating that they become activated by stress and serve to attenuate the stress-induced response of MRN 5-HT neurons.