Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat striatum

✍ Scribed by Marti Santiago; Esperanza R. Matarredona; Alberto Machado; Josefina Cano

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 119 KB
• Volume: 52
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19980601)52:5<591::aid-jnr11>3.0.co;2-5

✦ Synopsis

In vivo microdialysis was used to investigate the mechanism behind the increase in extracellular dopamine (DA) induced by increase in extracellular serotonin (5-HT) level and 5-HT 1 and 5-HT 2 receptor activation. The following serotoninergic drugs were perfused in the absence or presence of nomifensine (5 M)or tetrodotoxin (TTX; 2 M): clomipramine (10, 500 and 1,000 M), a selective 5-HT reuptake inhibitor; 8-OH-DPAT (50 and 500 M), a 5-HT 1A receptor agonist; and ␣-methyl-5-HT (1, 5 and 50 M), a 5-HT 2 receptor agonist. All the serotoninergic drugs studied increased DA extracellular output in a dosedependent manner. The presence of nomifensine attenuated the effect of perfusion of clomipramine (500 M) and completely abolished the effect of perfusion of 8-OH-DPAT (500 M) and ␣-methyl-5-HT (5 M) on DA extracellular output. Clomipramine (100-1,000 M) perfusion produced a dose dependent increase in DOPAC extracellular output, which was stronger when clomipramine (500 M) was co-perfused with nomifensine. 8-OH-DPAT and ␣-methyl-5-HT perfusion decreased DOPAC overflow. Addition of TTX to the perfusion fluid one hour before serotoninergic drugs perfusion, did not completely abolish the effect on dopamine extracellular output produced by the serotoninergic drugs. These data seem to indicate that increase in extracellular 5-HT level and 5-HT 1 and 5-HT 2 receptor activation increase in vivo DA extracellular output in the striatum mainly by a nonexocytotic mechanism involving DA uptake sites and, secondarily, by activation of 5-HT receptors.