Influence of excitatory amino acids on basal and sensory stimuli‐induced release of 5‐HT in the locus coeruleus

Abstract

The interactions between 5‐hydroxytryptaminergic neurones and excitatory amino acid utilizing neurones were studied in the locus coeruleus of conscious, freely moving rats. The locus coeruleus was superfused with artificial cerebrospinal fluid through a push‐pull cannula and 5‐hydroxytryptamine (5‐HT) was determined in the superfusate that was continuously collected in time periods of 10 min. Superfusion of the locus coeruleus with the NMDA receptor antagonist AP5 (10 μM), kynurenic acid (1 mM), or the AMPA/kainate receptor antagonist DNQX (10 μM) reduced the 5‐HT release in the locus coeruleus. Superfusion with the agonists NMDA (50 μM), kainic acid (50 μM) or AMPA (10 μM) enhanced the release rate of 5‐HT. AP5 (10 μM) blocked the stimulant effect of NMDA, while tetrodotoxin (1 μM) failed to influence the NMDA‐induced release of 5‐HT. In the presence of 10 μM DNQX, the releasing effect of 50 μM kainic acid was abolished. Pain elicited by tail pinch, as well as noise‐induced stress, increased the release of 5‐HT. Superfusion of the locus coeruleus with 10 μM AP5 reduced the tail pinch‐induced 5‐HT release. AP5 (10 μM) did not affect the noise‐induced release of 5‐HT which was reduced, when the locus coeruleus was superfused simultaneously with this concentration of AP5 and 1 μM kynurenic acid. DNQX (10 mM) failed to influence the release of 5‐HT induced by tail pinch or noise. The findings suggest that 5‐hydroxytryptaminergic neurones of the locus coeruleus are tonically modulated by excitatory amino acids via NMDA and AMPA/kainate receptors. The release of 5‐HT elicited by tail pinch and noise is mediated to a considerable extent through endogenous excitatory amino acids acting on NMDA receptors, while AMPA/kainate receptors are not involved in this process. British Journal of Pharmacology (1998) 123, 746–752; doi:10.1038/sj.bjp.0701656