Dopamine selectively reduces GABA(B) transmission onto dopaminergic neurones by an unconventional presynaptic action.
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 D(1)/D(2) dopamine receptor antagonists. A reduction of the GABA(B) IPSPs was also caused by noradrenaline (norepinephrine) and by L-beta-3,4-dihydroxyphenylalanine (L-DOPA), which is metabolically transformed into DA. The DA-induced depression of the IPSPs was partially antagonised by the alpha2 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, D(1) and D(2) 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.
Federici
Mauro
M
IRCCS-Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy.
Natoli
Silvia
S
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018080:Receptors, GABA-B / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014044:Tolbutamide / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D017447:Receptors, Dopamine D1; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D012701:Serotonin; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D014044:Tolbutamide; D015761:4-Aminopyridine; D004298:Dopamine