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Serotonin Stimulation of 5‐HT4 Receptors Indirectly Enhances In Vivo Dopamine Release in the Rat Striatum
Ist Teil von
Journal of neurochemistry, 1997-01, Vol.68 (1), p.195-203
Ort / Verlag
Oxford, UK: Blackwell Science Ltd
Erscheinungsjahr
1997
Quelle
Access via Wiley Online Library
Beschreibungen/Notizen
: Serotonin (5‐HT) applied at 1, 3, and 10 µM into the striatum of halothane‐anesthetized rats by in vivo microdialysis enhanced dopamine (DA) outflow up to 173, 283, and 584% of baseline values, respectively. The 5‐HT effect was partially reduced by 1 or 10 µM GR 125,487, a 5‐HT4 antagonist, and by 100 µM DAU 6285, a 5‐HT3/4 antagonist, whereas the 5‐HT1/2/6 antagonist methiothepin (50 µM) was ineffective. In the presence of tetrodotoxin the effect of 1 µM 5‐HT was not affected by 5‐HT4 antagonists. In addition, tetrodotoxin abolished the increase in DA release induced by the 5‐HT4 agonist (S)‐zacopride (100 µM). In striatal synaptosomes, 1 and 10 µM 5‐HT increased the outflow of newly synthesized [3H]DA up to 163 and 635% of control values, respectively. The 5‐HT4 agonists BIMU 8 and (S)‐zacopride (1 and 10 µM) failed to modify [3H]DA outflow, whereas 5‐methoxytryptamine (5‐MeOT) at 10 µM increased it (62%). In prelabeled [3H]DA synaptosomes, 1 µM 5‐HT, but not (S)‐zacopride (1 and 10 µM), increased [3H]DA outflow. DAU 6285 (10 µM) failed to modify the enhancement of newly synthesized [3H]DA outflow induced by 5‐MeOT or 5‐HT (1 µM), whereas the effect of 5‐HT was reduced to the same extent by the DA reuptake inhibitor nomifensine (1 µM) alone or in the presence of DAU 6285. These results show that striatal 5‐HT4 receptors are involved in the 5‐HT‐induced enhancement of striatal DA release in vivo and that they are not located on striatal DA terminals.