5-HT3 RECEPTOR AGONIST-INDUCED CARRIER-MEDIATED RELEASE OF DOPAMINE IN RAT STRIATUM IN-VIVO

1 In vivo microdialysis was used to study the effect of phenylbiguanide (PEG), a 5-hydroxytryptamine(3) receptor agonist, on the extracellular output of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the corpus striatum. 2 PEG produced a dose-related (10-500 mu M) increase in the release of dopamine (280-2000%). DOPAC and HVA output decreased with the perfusion of PEG. This decrease was similar with 50-500 mu M PEG. 5-HIAA output was not affected by any PEG concentration used. 3 When nomifensine (5 mu M) was included in the Ringer solution, the effect of PEG on the release of dopamine was ameliorated or inhibited. However, the effect of PEG (50-500 mu M) on the extracellular output of DOPAC and HVA was similar in the absence and in the presence of nomifensine (5 mu M). 4 Perfusion of MDL 72222, a 5-hydroxytryptamine(3) receptor antagonist, at doses of 50 and 100 mu M produced similar decreases (50% of controls) and increases (120% of controls) in the extracellular output of dopamine and DOPAC, respectively. HVA and 5-HIAA output levels were not affected by either concentration of MDL 72222. MDL 72222 (10 mu M) produced a slight and transient increase in the release of dopamine and a decrease in the extracellular output of DOPAC. HVA and 5-HIAA extracellular output was not affected by MDL 72222 (10 mu M) perfusion. 5 Go-perfusion of MDL 72222 (10 and 100 mu M) or tetrodotoxin (1 mu M) with PEG (50 mu M) did not modify the effect produced by PEG (50 mu M) alone on the release of dopamine. 6 These results suggest that the effect of PEG on the release of dopamine is mainly carrier-mediated.