PRESYNAPTIC INHIBITORY-ACTION OF OPIOIDS ON SYNAPTIC TRANSMISSION IN THE RAT PERIAQUEDUCTAL GREY IN-VITRO

1. The actions of opioids on synaptic transmission in rat periaqueduct al grey (PAG) neurones were examined using whole-cell patch-clamp reco rdings in brain slices. 2. Methionine enkephalin (ME; 10 mu M) inhibit ed evoked GABAergic inhibitory postsynaptic currents (IPSCs) by 57%, n on-NMDA excitatory postsynaptic currents (EPSCs) by 60%, and NMDA EPSC s by 43% in PAG neurones. This inhibition was associated with an incre ase in paired-pulse facilitation, was mimicked by the mu-agonist DAMGO (1-3 mu M) and abolished by naloxone (1 mu M). Neither the kappa-agon ist U69593 (1-3 mu M), nor the delta-agonist DPDPE (3-10 mu M) had any specific actions on evoked PSCs. 3. ME decreased the frequency of spo ntaneous 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 pe rsisted in nominally Ca2+-free, high-Mg2+ (10 mM) solutions, which als o contained Cd2+ (100 mu M), or Ba2+ (10 mM). Opioid inhibition of mIP SC frequency is unlikely to be mediated by presynaptic Ca2+ or K+ cond uctances which are sensitive to extracellular Cd2+ or Ba2+. 4. In a su bpopulation of PAG neurones, ME increased a Ba2+-sensitive K+ conducta nce at Potentials below -97 mV. Opioids inhibited both GABAergic and g lutamatergic synaptic transmission in all PAG neurones, independent of any postsynaptic opioid sensitivity. 5. These observations are consis tent with, but only partially support, the opioid disinhibition model of PAG-induced analgesia. mu-Opioids also have the potential to modula te the behavioural and autonomic functions of the PAG; via modulation of both inhibitory and excitatory presynaptic mechanisms, as well as p ostsynaptic mechanisms.