Muscimol, gamma-aminobutyric acidA receptors and excitatory amino acids in the mouse spinal cord.
These experiments examined the effects of intrathecally administered gamma-aminobutyric acid (GABA) agonists on the effects of intrathecally administered excitatory amino acid (EAA) agonists: N-methyl-D-aspartic acid (NMDA), quisqualic acid and kainic acid. We have found that muscimol, a GABAA receptor agonist, but not baclofen, a GABAB receptor agonist, dose-dependently inhibited caudally directed biting and scratching behavior induced by all three EAA agonists. This nonselective blockade of the expression of effects mediated by all three types of EAA receptor is in marked contrast to the selective blockade of NMDA effects seen previously in the case of mu opioids and phencyclidine receptor agonists. Inhibition by muscimol was blocked with the GABAA receptor antagonist, bicuculline. Decreased latency or hyperalgesia in the tail-flick test, found previously to be induced selectively by NMDA and blocked by an NMDA receptor antagonist, was similarly affected by muscimol but not baclofen, each given intrathecally. However, muscimol prolonged the tail-flick latency only after presentation of NMDA suggesting a possible antinociceptive effect of GABAA agonists in the presence of agonists at NMDA receptors. This study together with the preceding paper resolves GABA-mediated spinal antinociception into two components: a GABAA agonist selectively blocks nociception involving EAA receptors whereas a GABAB agonist selectively blocks substance P spinal activity (the preceding paper).
Aanonsen
L M
LM
University of Minnesota, Department of Pharmacology, Minneapolis.
Wilcox
G L
GL
D000698:Analgesia; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology*; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology
D010069:Oxadiazoles; D011963:Receptors, GABA-A; D009118:Muscimol; D001224:Aspartic Acid; D013373:Substance P; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D001418:Baclofen; D007608:Kainic Acid; D001640:Bicuculline