title: Presynaptic inhibitory action of opioids on synaptic transmission in the rat periaqueductal grey in vitro.
abstract: 1. The actions of opioids on synaptic transmission in rat periaqueductal grey (PAG) neurones were examined using whole-cell patch-clamp recordings in brain slices. 2. Methionine enkephalin (ME; 10 microM) inhibited evoked GABAergic inhibitory postsynaptic currents (IPSCs) by 57%, non-NMDA excitatory postsynaptic currents (EPSCs) by 60%, and NMDA EPSCs by 43% in PAG neurones. This inhibition was associated with an increase in paired-pulse facilitation, was mimicked by the mu-agonist DAMGO (1-3 microM) and abolished by naloxone (1 microM). Neither the kappa-agonist U69593 (1-3 microM), nor the delta-agonist DPDPE (3-10 microM) had any specific actions on evoked PSCs. 3. ME decreased the frequency of spontaneous miniature, action potential-independent postsynaptic currents (mIPSCs by 65%, mEPSCs by 54%) in all PAG neurones, but had no effect on their amplitude distributions. The reduction in mIPSC frequency persisted in nominally Ca(2+)-free, high-Mg2+ (10 mM) solutions, which also contained Cd2+ (100 microM), or Ba2+ (10 mM). Opioid inhibition of mIPSC frequency is unlikely to be mediated by presynaptic Ca2+ or K+ conductances which are sensitive to extracellular Cd2+ or Ba2+. 4. In a subpopulation of PAG neurones, ME increased a Ba(2+)-sensitive K+ conductance at potentials below -97 mV. Opioids inhibited both GABAergic and glutamatergic synaptic transmission in all PAG neurones, independent of any postsynaptic opioid sensitivity. 5. These observations are consistent with, but only partially support, the opioid disinhibition model of PAG-induced analgesia. mu-Opioids also have the potential to modulate the behavioural and autonomic functions of the PAG via modulation of both inhibitory and excitatory presynaptic mechanisms, as well as postsynaptic mechanisms.
authors.affiliation: Department of Pharmacology, University of Sydney, NSW, Australia. chrisv@anatomy.su.oz.au
authors.forename: C W
authors.initials: CW
authors.lastname: Vaughan
authors.forename: M J
authors.initials: MJ
authors.lastname: Christie
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid