Rotational behavior and electrophysiological effects induced by GABA(B) receptor activation in rat globus pallidus.
GABA is the major neurotransmitter used in the globus pallidus and there is evidence that GABA(B) receptors exist in this nucleus. Here we show that unilateral microinjection of baclofen, a GABA(B) receptor agonist, induced ipsilateral turning in Sprague-Dawley rats. This effect was prevented by preinjection of the GABA(B) receptor antagonist CGP55845A, which itself did not cause rotation. Thus, activation of GABA(B) receptor may suppress the activity of globus pallidus neurons, which is in line with the finding that the glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione also caused similar ipsilateral turning when injected into globus pallidus. Furthermore, in the presence of these glutamate receptor antagonists, injection of baclofen resulted in fewer rotations. To test the possibility that baclofen reduced glutamate release onto globus pallidus neurons, the effects of baclofen on miniature excitatory postsynaptic currents were studied in rat brain slices. Patch-clamp recordings showed that baclofen at 30 microM significantly reduced the frequency of the miniature excitatory postsynaptic currents. However, baclofen induced a weak outward current only in a minority of globus pallidus neurons. These pre- and postsynaptic effects of baclofen were reversed or prevented by CGP55845A. These results suggest that GABA(B) receptor in globus pallidus plays an important role in the regulation of movement by modulating glutamatergic inputs at a presynaptic site.
Chen
L
L
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, PR China.
Chan
S C Y
SC
Yung
W H
WH
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012399:Rotation; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D001418:Baclofen