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First published online on February 8, 2002.
 Copyright © 2002 by The Physiological Society
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2001.013938v1
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Received November 16, 2001
Accepted after revision January 4, 2002

Dopamine selectively reduces GABAB transmission onto dopaminergic neurones by an unconventional presynaptic action

Mauro Federici1, Silvia Natoli2, Giorgio Bernardi3, and N. B. Mercuri4*

1 * IRCCS-Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy
2 IRCCS-Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Istituto di Anestesia e Rianimazione Università di Roma-Tor Vergata, Rome, Italy
3 Clinica Neurologica Università di Roma-Tor Vergata, Rome, Italy
4 IRCCS-Fondazione Santa Lucia, Lab. di Neurologia Sperimentale, Via Ardeatina 306, 00179 Rome, Italy

* To whom correspondence should be addressed. E-mail: mercurin{at}med.uniroma2.it.

The functioning of midbrain dopaminergic neurones is closely involved in mental processes and movement. In particular the modulation of the inhibitory inputs on these cells might be crucial in controlling firing activity and dopamine (DA) release in the brain. Here, we report a concentration-dependent depressant action of dopamine on the GABAB IPSPs intracellularly recorded from dopaminergic neurones. Such effect was observed in spite of the presence of D1/D2 dopamine receptor antagonists. A reduction of the GABAB IPSPs was also caused by noradrenaline (norepinephrine) and by L-ß-3,4-dihydroxyphenylalanine (L-DOPA), which is metabolically transformed into DA. The DA-induced depression of the IPSPs was partially antagonised by the {alpha}2 antagonists yohimbine and phentolamine. DA did not change the postsynaptic effects of the GABAB agonist baclofen, suggesting a presynaptic site of action. Furthermore, DA did not modulate the GABAA-mediated IPSP. The DA-induced depression of the GABAB IPSP occluded the depression produced by serotonin and was not antagonized by serotonin antagonists. The DA- and 5-HT-induced depression of the GABAB IPSP persisted when calcium and potassium currents were reduced in to the presynaptic terminals. These results describe an unconventional presynaptic, D1 and D2 independent action of DA on the GABAB IPSP. This might have a principal role in determining therapeutic/side effects of L-DOPA and antipsychotics and could be also involved in drug abuse.




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