title: Opioid and GABA receptors involved in mediation and modulation of tonic and stimulus-evoked inhibition of a spinal reflex in the decerebrated and spinalized rabbit.
abstract: The purposes of this study were to investigate: (i) the identity of the opioid peptide(s) mediating tonic and stimulus-evoked inhibition of the sural-medial gastrocnemius reflex of the decerebrated, spinalized rabbit and (ii) the modulation of these processes by endogenous GABA. The selective delta receptor antagonist naltrindole (100 nmol kg(-1) i.v.), the GABA(A) blocker bicuculline (300 nmol intrathecal, i.th.), and the GABA(B) antagonist CGP 35348 (1 micromol i.th.) increased gastrocnemius reflexes to 150-160% of pre-drug values, whereas a sub-maximal dose of naloxone (30 nmol kg(-1) i.v.) augmented reflexes to >500% of controls. Kelatorphan, an inhibitor of enkephalin metabolism (2 micromol i.th.), depressed gastrocnemius responses by 50% and potentiated the inhibitory effects of methionine enkephalin. Repetitive electrical stimulation of the superficial or common peroneal nerves inhibited reflexes for 15-20 min. This effect was significantly reduced by naltrindole and CGP 35348. It was not reduced by a low dose (30 nmol kg(-1) i.v.) of naloxone or by bicuculline. When naloxone and naltrindole were combined at 30 nmol kg(-1) each, stimulus-evoked inhibition was blocked. Given after bicuculline, naloxone at 100 nmol kg(-1) i.v. abolished peroneal-evoked inhibition, but a dose of 300 nmol kg(-1) was required to produce the same effect after CGP 35348. Kelatorphan augmented the depth and duration of inhibition evoked by peroneal nerve stimulation. These data are consistent with the involvement of enkephalin-like peptides in tonic and stimulus-evoked inhibition of the sural-gastrocnemius reflex. Tonic inhibition in rabbit spinal cord is dominated by opioids acting through mu receptors, whereas co-activation of delta, mu and GABA(B) receptors mediates stimulus-evoked inhibition. It is possible that GABA(B) receptors inhibit the release of spinal opioids while simultaneously supporting their actions at post-synaptic targets.
authors.affiliation: Division of Animal Physiology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK. robert.clarke@nottinham.ac.uk
authors.forename: R W
authors.initials: RW
authors.lastname: Clarke
authors.forename: R N
authors.initials: RN
authors.lastname: Bhandari
authors.forename: J
authors.initials: J
authors.lastname: Leggett
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011817:Rabbits; D018079:Receptors, GABA / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*
chemical_list: D018756:GABA Antagonists; D009292:Narcotic Antagonists; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; D009270:Naloxone; D004744:Enkephalin, Methionine; D009271:Naltrexone; C066430:CGP 35348; C055382:naltrindole; D001640:Bicuculline