title: Disinhibition of spinal responses to primary afferent input by antagonism at GABA receptors in urethane-anaesthetised rats is dependent on NMDA and metabotropic glutamate receptors.
abstract: Disruption of spinal GABAergic circuits, which regulate the conveyance of sensory information to spinal cord neurones from the primary afferent system, leads to miscoding of afferent input and often results in hyperresponsiveness states. In the present work, extracellular field potentials elicited by electrical peripheral nerve activation were recorded in the urethane-anaesthetised rat following spinal administration of GABA(A) or GABA(B) receptor-antagonists, and the involvement of glutamate receptors of the NMDA and metabotropic types in changes induced by altered GABAergic function was examined by pre-treating the spinal dorsal horn with appropriate antagonist drugs. Spinal administration of the GABA(A) receptor antagonist bicuculline (BIC) dose-dependently augmented poly- but not monosynaptic field potentials elicited by activation of A fibres or potentials elicited by activation of C fibres, whereas application of the GABA(B) receptor antagonist CGP35348 significantly increased the amplitudes of C- but not A fibre-evoked potentials. BIC-induced augmentation was blocked by pre-treatment with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) or the group I or II metabotropic glutamate receptor (mGluR)-antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) or (2S)-alpha-ethylglutamic acid (EGLU), respectively, but not by the group III mGluR-antagonist (RS)-alpha-methylserine-O-phosphate (MSOP). Augmentation of spinal field potentials induced by CGP35348 was prevented by pre-treatment with D-AP5 but not with mGluR-antagonists. The present findings provide novel evidence that disparate synaptic mechanisms subserved by metabotropic and NMDA glutamate receptors may be involved in spinal hyperresponsiveness states secondary to decreased GABA(A) or GABA(B) receptor activity.
authors.affiliation: Department of Neurosciences, School of Medicine and Dentistry, Basque Country University, Barrio Sarriena s/n, 48940 Leioa, Spain.
authors.forename: Itsaso
authors.initials: I
authors.lastname: Buesa
authors.forename: Vicente
authors.initials: V
authors.lastname: Ortiz
authors.forename: Luciano
authors.initials: L
authors.lastname: Aguilera
authors.forename: Fernando
authors.initials: F
authors.lastname: Torre
authors.forename: Manfred
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Jon Jatsu
authors.initials: JJ
authors.lastname: Azkue
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018079:Receptors, GABA / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects*; D014520:Urethane / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D014520:Urethane; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C066430:CGP 35348; D001640:Bicuculline