In vivo and ex vivo studies in which the involvement of 5-HT heteroreceptors in modulation of DA release has been investigated Effects of various drugs acting at different levels of the 5-HT system on DA release determined in microdialysis studies of the rat or mouse nigrostriatal or mesocortical DA system are shown. Unless stated otherwise, the drugs were applied by the probe perfusion fluid. As a rule, the results did not allow clear-cut statements concerning the receptor type(s) involved. 5-HT receptor localization on interneurons as a rule is probable.
| Species | Brain Region | Receptor Type | Drugs | Release-Increasing Concentration | Comment | References |
|---|---|---|---|---|---|---|
| Rat | Striatum | 5-HT | 4 × 10–11–4 × 10–9 M | In vivo microdialysis in anesthetized (with chloral hydrate) rats; pindolol (4 nmol/40 μl fraction) inhibited the 5-HT (0.4 nmol/40 μl fraction)-evoked increase in DA release | Benloucif and Galloway (1991) | |
| mCPP | 4 × 10–10–4 × 10–8 M | |||||
| TFMPP | 10–8–1.6 × 10–7 M | |||||
| RU 24969 | 2 × 10–9 M | |||||
| 8-OH-DPAT | 2 × 10–9 M | |||||
| Fenfluramine | 4 × 10–10–4 × 10–8 M | |||||
| Rat | Striatum | TFMPP | 3–30 mg/kg | Ex vivo determination of 3-MTa as an indirect parameter for DA release in vivo with HPLC in homogenates of striatal tissue; 3-MT, TFMPP, or ritanserin applied by s.c. injection; ritanserin without effect | Nissbrandt et al. (1992) | |
| Rat | Striatum | 5-HT1, 5-HT3 | 5-HT | 10–5–10–4 M | In vivo microdialysis in anesthetized rats; drugs applied by probe perfusion; pindolol (4 nmol/40 μl fraction) reduced the effect of RU 24969 (2 nmol/40 μl fraction); ICS 205,930 (4 nmol/40 μl fraction), and MDL 72222 (4 nmol/40 μl fraction) reduced the facilitatory effect of 5-HT; ritanserin without effect; involvement of 5-HT1 and 5-HT3, but not of 5-HT2, receptors suggested | Benloucif et al. (1993) |
| RU 24969 | 3 × 10–5–3 × 10–4 M | |||||
| 5-MeOT | 3 × 10–4–3 × 10–3 M | |||||
| 8-OH-DPAT | 10–4–3 × 10–3 M | |||||
| DOI | 3 × 10–4–3 × 10–3 M | |||||
| Rat | Striatum | 5-HT | 10–6–10–5 M DA, DOPAC, and HVA increased | In vivo microdialysis in freely moving rats; 5-HT, 5-HIAA, DA, DOPAC, and HVA determined in the dialysate; drugs; 5,7-DHT pretreatment abolished the effect of the 5-HT uptake inhibitor alaproclate on dialysate levels of DA | Yadid et al. (1994) | |
| Alaproclatee | ||||||
| CGS 12066B | 4 × 10–4 M | |||||
| 10–6 M | ||||||
| Rat | Medial prefrontal cortex | 5-HT2A | MDL 100,907 | 0.1–1 mg/kg s.c. or 10–6 M directly i.c.v. | In vivo microdialysis in freely moving rats; ritanserin (2.5 mg/kg s.c.) without effect; 5-HT2A receptors probably involved, but location on interneurons probable | Schmidt and Fadayel (1995) |
| Mouse 5-HT1B ko | Dorsal striatum | CP-93,129 | 5 × 10–5 M: 5-fold increase | In vivo microdialysis in anesthetized mice; CP-93,129 increased DA release in 5-HT1B ko and in wild-type mice | De Groote et al. (2003) |
3-MT, 3-methoxytryptamine (dopamine metabolite); HPLC, high-pressure liquid chromatography; 5-MeOT, 5-methoxytryptamine (5-HT4 agonist); DOPAC, 3,4-dihydroxyphenylacetic acid (dopamine metabolite); HVA, homovanillic acid (catecholamine metabolite); 5-HIAA, 5-hydroxyindoleacetic acid (5-HT metabolite); ko, knockout
↵ a Accumulation of the DA metabolite 3-MT formed by catechol-O-methyltransferase after inhibition of monoamine oxidase by pargyline was used as an indirect measure of dopamine release and metabolism in vivo
↵ b 5-HT reuptake blocker