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

Mauro Federici *, Silvia Natoli *†, Giorgio Bernardi *‡ and Nicola B. Mercuri *‡

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 GABA_B 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 GABA_B IPSPs was also caused by noradrenaline (norepinephrine) and by L--3,4-dihydroxyphenylalanine (L-DOPA), which is metabolically transformed into DA. The DA-induced depression of the IPSPs was partially antagonised by the 2 antagonists yohimbine and phentolamine. DA did not change the postsynaptic effects of the GABA_B agonist baclofen, suggesting a presynaptic site of action. Furthermore, DA did not modulate the GABA_A-mediated IPSP. The DA-induced depression of the GABA_B IPSP occluded the depression produced by serotonin and was not antagonized by serotonin antagonists. The DA- and 5-HT-induced depression of the GABA_B 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 GABA_B 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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