To test whether endogenously released opioids also inhibit local GABA synapses, we used either the low or moderate stimulus protocol together with the peptidase inhibitor cocktail. When we used the moderate stimulus, peptidase inhibitors significantly decreased eIPSC amplitude of the test pulse (13.1±5.2% inhibition, P<0.05 versus baseline, paired t-test, for example, Fig. 6j), which was then significantly increased by naloxone (Fig. 6j,k). However, when the low stimulus was used, neither the peptidase inhibitor cocktail (10.1±6.0% inhibition, n=6, P>0.05 versus baseline, paired t-test) nor naloxone (Fig. 6k) significantly changed eIPSC amplitude. Thus local GABAergic synapses within Im are inhibited by endogenously released opioids but only with a combination of PIs and the moderate stimulus and even then, only to a modest extent. This is somewhat surprising considering the strong regulation of these synapses by exogenous ME. In fact, while endogenously released opioids inhibit the BLA-ITC synapse to almost 50% of the maximal opioid inhibition of this synapse, at local ITC GABAergic synapses, it is <15%. This difference could be due to less effective stimulation of endogenous opioid release when studying GABAergic synapses and may indicate a requirement for intact glutamatergic signalling. Alternatively, this difference may result from other ultrastructural differences such as receptor location relative to dense core vesicle release sites.