Opioid-Induced Reductions in Amygdala Lateral Paracapsular GABA Neuron Circuit Activity

Opioid use and withdrawal evokes behavioral adaptations such as drug seeking and anxiety, though the underlying neurocircuitry changes are unknown. The basolateral amygdala (BLA) regulates these behaviors through principal neuron activation. Excitatory BLA pyramidal neuron activity is controlled by feedforward inhibition provided, in part, by lateral paracapsular (LPC) GABAergic inhibitory neurons, residing along the BLA/external capsule border. LPC neurons express mu-opioid receptors (MORs) and are potential targets of opioids in the etiology of opioid-use disorders and anxiety-like behaviors. Here, we investigated the effects of opioid exposure on LPC neuron activity using immunohistochemical and electrophysiological approaches. We show that LPC neurons, and other nearby BLA GABA and non-GABA neurons, express MORs and delta-opioid receptors. Additionally, DAMGO, a selective MOR agonist, reduced GABA but not glutamate-mediated spontaneous postsynaptic currents in LPC neurons. Furthermore, in LPC neurons, abstinence from repeated morphine-exposure in vivo (10 mg/kg/day, 5 days, 2 days off) decrease the intrinsic membrane excitability, with a similar to 75% increase in afterhyperpolarization and similar to 40-50% enhanced adenylyl cyclase-dependent activity in LPC neurons. These data show that MORs in the BLA are a highly sensitive targets for opioid-induced inhibition and that repeated opioid exposure results in impaired LPC neuron excitability.

Automated summary

Opioid use and withdrawal can lead to behavioral adaptations, such as drug seeking and anxiety. The basolateral amygdala (BLA) controls these behaviors through the activation of principal neurons. The study found that lateral paracapsular (LPC) GABAergic inhibitory neurons, which express mu-opioid receptors (MORs), are potential targets in opioid-use disorders and anxiety-like behaviors. The research also demonstrated that repeated opioid exposure impairs the excitability of LPC neurons.