Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro.
Previous studies suggested that the postsynaptic GABA(B) receptors of deep cerebellar nuclear neurons of adult rats were not activated by selective GABA(B) receptor agonist baclofen or endogenous GABA released by cerebellar cortical Purkinje cells, although the receptors have been demonstrated to exist in the deep cerebellar nuclei. In this study, cerebellar slices of adult rats were prepared for testing effects of GABA, baclofen and muscimol (selective GABA(A) receptor agonist) on cerebellar interpositus nucleus (IN) neurons. Perfusing slices with GABA (10-1000 microM), baclofen (1-30 microM) and muscimol (1-100 microM) respectively produced a dose-dependent inhibitory response on the IN neurons (n = 39, 62 and 50), which was not blocked by low-Ca(2+)/high-Mg(2+) medium (n = 5, 6 and 6), supporting a direct postsynaptic action of these GABAergic agonists. Moreover, both selective GABA(B) receptor antagonist CGP35348 and selective GABA(A) receptor antagonist bicuculline were capable of partially blocking the inhibitory response of IN neurons to GABA (n = 14 and 11), suggesting that the GABA-induced inhibition may contain two components, a GABA(B) receptors-mediated component and a GABA(A) receptors-mediated one. Further experiments revealed that not only muscimol (n = 50) but also baclofen (n = 62) suppressed IN cells' activity. The baclofen-induced inhibition was selectively blocked by CGP35348 (n = 12) but not by bicuculline (n = 8), whereas the muscimol-induced inhibition was selectively antagonized by bicuculline (n = 8) instead of CGP35348 (n = 9). These results indicate that GABA(B) receptors in the IN neurons can be activated not only by GABA but also by baclofen, suggesting that besides GABA(A) receptors, GABA(B) receptors may also be involved in mediating the inhibitory effect of GABA on cerebellar IN neurons of adult rats.
Chen
Kun
K
Department of Biological Science and Technology, School of Life Sciences, Mailbox 426, Nanjing University, China.
Li
Hong-Zhao
HZ
Ye
Na
N
Zhang
Jun
J
Wang
Jian-Jun
JJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002529:Cerebellar Nuclei / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen; D008274:Magnesium; D002118:Calcium; D001640:Bicuculline