Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs

Abstract

Kappa opioid receptors (KORs) have been implicated in anxiety and stress, conditions that involve activation of projections from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in several brain regions, their role on mPFC physiology and on BLA projections to the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs from the BLA to the mPFC using in vivo electrophysiological recordings with electrical and optogenetic stimulation. Systemic administration of the KOR agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without altering hippocampus-evoked responses. IntramPFC U69,593 inhibited electrical and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI increased center time in the open field test, suggesting an anxiolytic effect. The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings provide a framework whereby KOR signaling during stress and anxiety can regulate the flow of emotional state information from the BLA to the mPFC.

Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

“…As BLA terminal expression is “patchy” in the dorsomedial NAcc shell and KOR inhibition of glutamate release is strongest in this region, it is possible that there is at least one more KOR-sensitive input to the shell. BLA afferents in the prefrontal cortex and bed nucleus of the stria terminalis are inhibited by KORs (Crowley et al, 2016; Tejeda et al, 2015), suggesting that presynaptic modulation of BLA output is a shared principle among different BLA efferents. Interestingly, baclofen inhibited both VH- and BLA-evoked oEPSCs suggesting that NAcc GABA-B receptors may not confer the same pathway specificity as KORs.…”

Predicting personality from network-based resting-state functional connectivity

“…; Allen and DeYoung 2016) and its genetic variation has been also pointed to the opiate system, due to its involvement in the hedonic response to the stimulus (Peciña et al 2006). It is, therefore, possible that the endogenous opioid system via modulation of amygdala and medial prefrontal cortex (Tejeda et al 2015; Selleck and Baldo 2017), most used regions in the connections of Face , mediate both the perception of faces (Martin et al 2006) and the social bonding (Pasternak and Pan 2013). We thus suggest that functional connectivity within the Face network in Men is mostly related to the “Affiliative” aspect of Extraversion.…”

Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of Ethanol

“…Additionally, as KORs residing on locus coeruleus noradrenergic (Kreibich et al., ) and dorsal raphe serotonergic (Land et al., ) neurons modulate ascending monoaminergic transmission, adaptations in these pathways likely influence motivational effects of EtOH as well as affective behaviors associated with chronic EtOH exposure and withdrawal. Within the prefrontal cortex, KORs have been shown to mediate glutamatergic and dopaminergic signaling (Tejeda et al., , ). However, the role of DYN/KOR activity in cortical regions has not been studied with regard to EtOH‐related behaviors.…”