Dopamine depletion alters responses to glutamate and GABA in the rat subthalamic nucleus.
We used whole-cell recordings to compare currents evoked by glutamate and GABA receptor agonists in subthalamic nucleus neurons located ipsilateral and contralateral to unilateral 6-hydroxydopamine (6-OHDA) injections into the substantia nigra zona compacta. The ratio of currents evoked by AMPA (0.6 microM) and NMDA (20 microM) was significantly greater in neurons recorded ipsilateral to 6-OHDA lesions compared with the ratio of currents recorded in control (contralateral) neurons. Both the GABA(A) agonist isoguvacine (20 microM) and the GABA(B) agonist baclofen (10 microM) evoked significantly greater outward currents in subthalamic nucleus neurons ipsilateral to the lesion compared to contralateral neurons. We conclude that chronic dopamine depletion up-regulates expression of GABA receptors and shifts the functional expression of ionotropic glutamate receptor subtype from NMDA to AMPA receptors in subthalamic nucleus.
Shen
Ke-Zhong
KZ
1Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
Johnson
Steven W
SW
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000096:biosynthesis; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*
D018755:GABA Agonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016627:Oxidopamine; D004298:Dopamine