Intrathecal GABAB antagonists attenuate the antinociception produced by microinjection of L-glutamate into the ventromedial medulla of the rat.
This study examined whether the antinociception produced by glutaminergic stimulation of neurons in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (NGCp alpha) is mediated by an action of GABA at GABAB receptors in the spinal cord. Rats were pretreated with intrathecal (i.t.) administration of the selective GABAB receptor antagonists phaclofen (100 micrograms) or CGP 35348 (30 micrograms), the serotonin receptor antagonist methysergide (30 micrograms), or vehicle. Fifteen min later, 30 nmol L-glutamate was microinjected into the NRM, NGCp alpha, or sites in the medulla outside these two regions. Microinjection of L-glutamate into the NRM or NGCp alpha in vehicle-pretreated rats significantly increased tail flick latency. This increase was antagonized, but not abolished, by i.t. pretreatment with 30 micrograms CGP 35348 or 100 micrograms phaclofen. Pretreatment with 30 micrograms methysergide completely antagonized the antinociception produced by L-glutamate. Microinjection of L-glutamate at medullary sites outside the NMR or NGCp alpha did not produce antinociception. In an ancillary experiment, the possibility that the ability of methysergide, phaclofen or CGP 35348 to antagonize glutamate-induced antinociception was related to non-specific increases in tail skin temperature was explored. Although phaclofen or methysergide increased tail skin temperature, the magnitude and time course of this increase were not consistent with the antagonism of glutamate-induced antinociception. Moreover, administration of CGP 35348 resulted in a modest decrease in tail skin temperature. Thus, antagonism of glutamate-induced antinociception does not appear to result from non-specific alterations in tail skin temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
McGowan
M K
MK
Department of Anesthesia and Critical Care, University of Chicago, IL 60637.
Hammond
D L
DL
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001479:Basal Ganglia / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D005971:Glutamates / Q000008:administration & dosage; D018698:Glutamic Acid; D007278:Injections, Spinal; D008526:Medulla Oblongata; D008784:Methysergide / Q000008:administration & dosage / Q000494:pharmacology; D008845:Microinjections; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects
D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D005971:Glutamates; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; C052329:phaclofen; D018698:Glutamic Acid; C066430:CGP 35348; D001418:Baclofen; D008784:Methysergide