Neural circuits in the amygdala are important for associating the positive experience of drug taking with the coincident environmental cues. During abstinence, cue re-exposure activates the amygdala, increases dopamine release in the amygdala and stimulates relapse to drug use in an opioid dependent manner. Neural circuits in the amygdala and the learning that underlies these behaviours are inhibited by GABAergic synaptic inhibition. A specialised subtype of GABAergic neurons in the amygdala are the clusters of intercalated cells. We focussed on the main-island of intercalated cells because these neurons, located ventromedial to the basolateral amygdala, express very high levels of dopamine D1-receptor and μ-opioid receptor, release enkephalin and are densely innervated by the ventral tegmental area. However, where these neurons project to was not fully described and their regulation by opioids and dopamine was incomplete. To address this issue we electrically stimulated in the main-island of the intercalated cells in rat brain slices and made patch-clamp recordings of GABAergic synaptics from amygdala neurons. We found that main-island neurons had a strong GABAergic inhibitory output to pyramidal neurons of the basolateral nucleus and the medial central nucleus, the major output zones of the amygdala. Opioids inhibited both these synaptic outputs of the intercalated neurons and thus would disinhibit these target zones. Additionally, dopamine acting at D1-receptors inhibited main-island neuron synapses onto other main-island neurons. This data indicates that the inhibitory projections from the main-island neurons could influence multiple aspects of addiction and emotional processing in an opioid and dopamine dependent manner.
Keywords: addiction; enkephalin; rat; synaptic modulation.
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.