Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine release in the rat striatum.
Serotonin (5-HT) applied at 1, 3, and 10 microM 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 microM GR 125,487, a 5-HT4 antagonist, and by 100 microM DAU 6285, a 5-HT3/4 antagonist, whereas the 5-HT1/2/6 antagonist methiothepin (50 microM) was ineffective. In the presence of tetrodotoxin the effect of 1 microM 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 microM). In striatal synaptosomes, 1 and 10 microM 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 microM) failed to modify [3H]DA outflow, whereas 5- methoxytryptamine (5-MeOT) at 10 microM increased it (62%). In prelabeled [3H]DA synaptosomes, 1 microM 5-HT, but not (S)-zacopride (1 and 10 microM), increased [3H]DA outflow. DAU 6285 (10 microM) failed to modify the enhancement of newly synthesized [3H]DA outflow induced by 5-MeOT or 5-HT (1 microM), whereas the effect of 5-HT was reduced to the same extent by the DA reuptake inhibitor nomifensine (1 microM) 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.
De Deurwaerdère
P
P
Université de Bordeaux II, INSERM U. 259, Bordeaux, France.
L'hirondel
M
M
Bonhomme
N
N
Lucas
G
G
Cheramy
A
A
Spampinato
U
U
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018765:Dopamine Uptake Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D009627:Nomifensine; D012701:Serotonin; D013779:Tetrodotoxin; C055971:zacopride; D004298:Dopamine