Opioid Withdrawal Abruptly Disrupts Amygdala Circuit Function by Reducing Peptide Actions.

While the physical signs of opioid withdrawal are most readily observable, withdrawal insidiously drives relapse and contributes to compulsive drug use, by disrupting emotional learning circuits. How these circuits become disrupted during withdrawal is poorly understood. Because amygdala neurons mediate relapse, and are highly opioid sensitive, we hypothesized that opioid withdrawal would induce adaptations in these neurons, opening a window of disrupted emotional learning circuit function.

Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control.

Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan.

Dopamine and opioids inhibit synaptic outputs of the main island of the intercalated neurons of the amygdala.

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.

Endogenous opioids regulate moment-to-moment neuronal communication and excitability.

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster.