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Depression of mGluR‐mediated IPSCs by 5‐HT in dopamine neurons of the rat substantia nigra pars compacta
Author(s) -
Paolucci E.,
Berretta N.,
Tozzi A.,
Bernardi G.,
Mercuri N. B.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2003.03015.x
Subject(s) - pars compacta , substantia nigra , dopamine , neuroscience , metabotropic glutamate receptor , dopaminergic , chemistry , biology , agonist , receptor , biochemistry
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 (mGluR‐IPSC) in midbrain dopamine neurons, and we found a reversible depression of this synaptic response at concentrations of 5‐HT ranging from 100 n m to 30 µ m (EC 50 1.06 µ m ). 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 Ca 2+ ‐sensitive K + conductances underlying the mGluR‐IPSC, but was associated with a decrease in the intracellular calcium signal triggered by mGluR stimulation. Similar results were obtained with α‐methyl‐5‐hydroxytryptamine and 5‐methoxytryptamine, but not with 5‐carboxamidotryptamine or 1‐(3‐chlorophenyl) piperazine. No significant depression of the mGluR‐IPSC by 5‐HT was observed in the presence of the 5‐HT 2 antagonist cinanserin or the 5‐HT 4 receptor antagonist RS 23597–190, whereas the 5‐HT 2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful inhibition of the mGluR‐IPSC by 5‐HT in midbrain dopamine neurons, most probably through stimulation of 5‐HT 2A and 5‐HT 4 receptors.