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

被引:16
作者
Federici, M
Natoli, S
Bernardi, G
Mercuri, NB
机构
[1] IRCCS, Fdn Santa Lucia, Lab Neurol Sperimentale, I-00179 Rome, Italy
[2] Univ Roma Tor Vergata, Ist Anestesia & Rianimaz, Rome, Italy
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2002年 / 540卷 / 01期
关键词
D O I
10.1113/jphysiol.2001.013938
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 GABAB IPSPs was also caused by noradrenaline (norepinephrine) and by L-,beta-3,4-dihydroxyphenylaianine (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 GABAB agonist baclofen, suggesting a presynaptic site of action. Furthermore, DA did not modulate the GABA(A)-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, D, 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.
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页码:119 / 128
页数:10
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