Depression of mGluR-mediated IPSCs by 5-HT in dopamine neurons of the rat substantia nigra pars compacta

E. Paolucci, N. Berretta, A. Tozzi, G. Bernardi, N. B. Mercuri

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Dopamine neurons of the substantia nigra pars compacta receive a prominent serotonin (5-HT) projection from the dorsal raphe nucleus and important functional interactions between the serotonergic and the dopaminergic system have been postulated. In the present report we examined the role of 5-HT in the modulation of the metabotropic glutamate receptor-mediated inhibitory postsynaptic current (mGIuR-IPSC) in midbrain dopamine neurons, and we found a reversible depression of this synaptic response at concentrations of 5-HT ranging from 100 nM to 30 μM (EC50 1.06 μM). This resulted in a shift towards excitation of the overall dopamine neuron response to glutamatergic synaptic input. This effect was not because of a direct modulation of the Ca2+-sensitive K+ conductances underlying the mGIuR-IPSC, but was associated with a decrease in the intracellular calcium signal triggered by mGluR stimulation. Similar results were obtained with α-5-hydroxytryptamine and 5-methoxytryptamine, but not with 5-carboxamidotryptamine or 1-(3-chlorophenyl) piperazine. No significant depression of the mGIuR-IPSC by 5-HT was observed in the presence of the 5-HT2 antagonist cinanserin or the 5-HT4 receptor antagonist RS 23597-190, whereas the 5-HT2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful inhibition of the mGIuR-IPSC by 5-HT in midbrain dopamine neurons, most probably through stimulation of 5-HT2A and 5-HT4 receptors.

Original languageEnglish
Pages (from-to)2743-2750
Number of pages8
JournalEuropean Journal of Neuroscience
Issue number10
Publication statusPublished - Nov 2003



  • 5-HT receptors
  • 5-HT receptors
  • Basal ganglia
  • SK channels

ASJC Scopus subject areas

  • Neuroscience(all)

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