Studies in which the involvement of presynaptic 5-HT heteroreceptors in direct modulation of GABA release has been investigated Effects of various 5-HT receptor ligands and p-chloramphetamine on GABA release in various brain regions of rodent and human brain are shown.
| Species | Brain Region | Receptor Typea | Drugs | Release-Modifying Concentration or Dose | Comment | References |
|---|---|---|---|---|---|---|
| Rat, Wistar | Basolateral amygdala | 5-HT1A | 8-OH-DPAT | 10–6 M: inhibition | Whole-cell voltage-clamp recording from acutely mechanically dissociated neurons with adherent GABAergic synaptic boutons (synaptic bouton preparation); spontaneous GABAergic mIPSPs determined | Koyama et al. (1999) |
| Rat, Wistar | Basolateral amygdala | 5-HT1A | 8-OH-DPAT | 10–6 M: inhibition | Whole-cell voltage-clamp recording from acutely mechanically dissociated neurons; synaptic bouton preparation; spontaneous GABAergic mIPSPs | Koyama et al. (2002) |
| Rat, Wistar | Hippocampus CA1 | 5-HT1A | 8-OH-DPAT | 10–6 M: inhibition | Whole-cell voltage-clamp recording from acutely mechanically dissociated CA1 pyramidal neurons; synaptic bouton preparation; electrical stimulation of single boutons | Katsurabayashi et al. (2003) |
| Human | Neocortex | “5-HT1D”b | Sumatriptan | 10–7–10–5 M: inhibition | Superfusion of slices; methiothepine (10–6 M) prevented inhibition by sumatriptan | Feuerstein et al. (1996) |
| Rat | Ventral tegmental area | 5-HT1B | CP-93129 | 1.5–4.5 × 10–7 M: inhibition | Superfusion of slices in the presence of nipecotic acid and aminooxyacetic acid; SB 216641 prevented inhibition; 8-OH-DPAT and WAY100635 without effect | Yan and Yan (2001) |
| RU 24969 | 1.5–4.5 × 10–7 M: inhibition | |||||
| Rat mouse | Suprachiasmatic nucleus | 5-HT1B | CP-93129 | 10–6 M: inhibition | Frequency, but not amplitude, of mIPSPs recorded in suprachiasmatic nucleus neurons decreased in wild-type mice, yet no effect of CP-93129 in 5-HT1B receptor knockout mice | Bramley et al. (2005) |
| Rat ♂ | Neocortex | 5-HT2A | DOI | 10–6 M: increase | Superfusion of synaptosomes, GABA release determined; trazodone (10–10–10–6 M) antagonized effect of DOI | Luparini et al. (2004) |
| Rat | Caudate putamen | 5-HT3 | p-Chloramphetamine | 10–7 M: facilitation | Superfusion of slices; determination of the enhancing effect of p-chloramphetamine on K+ (20 mM)-evoked of [3H]GABA release; effect of p-chloramphetamine blocked by ICS 205,930 (5 × 10–8 M) or MDL 72222 (10–7 M) | Meyer et al. (1991) |
| Rat, Wistar | Basolateral amygdala neurons | 5-HT3 | mCPBG | 10–6 M: facilitation | Whole-cell voltage-clamp recording from acutely mechanically dissociated basolateral amygdala neurons; synaptic bouton preparation; spontaneous GABAergic mIPSPs | Koyama et al. (2000) |
| Rat, Wistar | Basolateral amygdala | 5-HT3 | mCPBG | 10–6 M: facilitation | Whole-cell voltage-clamp recording from acutely mechanically dissociated basolateral amygdala neurons; synaptic bouton preparation; synaptic bouton preparation; spontaneous GABAergic mIPSPs | Koyama et al. (2002) |
| Rat, Wistar | Hippocampus | 5-HT3 | mCPBG | 1–3 × 10–6 M: facilitation | Whole-cell voltage-clamp recording from acutely mechanically dissociated CA1 pyramidal neurons; synaptic bouton preparation; electrical stimulation of single boutons | Katsurabayashi et al. (2003) |
| Rat, Sprague-Dawley | Hippocampus | 5-HT3 | 5-HT | 5 × 10–5–10–4 M: facilitation | Whole-cell voltage-clamp recording from CA1 pyramidal neurons in hippocampal slices; 5-HT elicited GABAergic mIPSPs blocked by ICS 205,930 (2 × 10–9 M) but not by TTX | Turner et al. (2004) |
| mCPBG | 10–6 M: facilitation | |||||
| Mouse | 5-HT3 | 5-HT mCPBG | 10–4 M: facilitation | Superfusion of synaptosomes prelabeled with [3H]GABA; osmotically by 0.5 M sucrose evoked release of [3H]GABA; 5-HT effect blocked by ICS 205,930 (10–6 M) | Turner et al. (2004) | |
| Hippocampus | 10–5 M: facilitation | |||||
| Rat | Cultured hippocampal neurons | 5-HT3 | 5-HT | 10–5 M: stimulation | Whole-cell patch-clamp recordings from single neuron microcultures that form autapses; ICS 205,930 3 × 10–7 M abolished the effect of 5-HT | Dorostkar and Boehm (2005, 2007) |