GABA(A) and GABA(B) antagonists differentially affect the firing pattern of substantia nigra dopaminergic neurons in vivo.
The effects of local pressure application of the selective GABA(A) antagonists, bicuculline, gabazine, and picrotoxin, and the selective GABA(B) antagonists, 2-OH-saclofen and CGP-55845A, on the spontaneous activity of electrophysiologically identified substantia nigra dopaminergic neurons were recorded in vivo in urethane anesthetized rats. Blockade of GABA(A) inputs by bicuculline powerfully and reversibly induced burst firing in dopaminergic neurons along with a modest (25%) increase in firing rate, but the increase in burst firing was not correlated with the increase in firing rate. Picrotoxin and gabazine also produced an increase in burst firing without an increase in firing rate. In contrast, local application of GABA(B) antagonists did not produce bursting but rather caused a modest shift to a more regular firing pattern in 50% of the cases. These data demonstrate that dopaminergic neurons in vivo are under tonic GABAergic inhibition mediated by GABA(A) receptors and suggest that GABAergic afferents to substantia nigra comprise a major pathway by which the firing pattern of dopaminergic neurons is controlled in vivo.
Paladini
C A
CA
Aidekman Research Center, Rutgers, The State University of New Jersey, Newark 07102, USA.
Tepper
J M
JM
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D001418:Baclofen; D001640:Bicuculline; D004298:Dopamine; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D011412:Propanolamines; D011724:Pyridazines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C085075:CGP 55845A; C049853:gabazine; C057491:2-hydroxysaclofen