title: 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. Intra-mPFC 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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Tejeda
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Hanks
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: Liam
authors.initials: L
authors.lastname: Scott
authors.affiliation: Neuronal Networks Section, National Institute on Drug Abuse, Baltimore, MD, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Mejias-Aponte
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: Zoë A
authors.initials: ZA
authors.lastname: Hughes
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.|Neuroscience and Pain Research Unit, Pfizer, Cambridge, MA, USA.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Patricio
authors.initials: P
authors.lastname: O'Donnell
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000502:physiology*; D044482:Benzeneacetamides / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D011897:Random Allocation; D020318:Rats, Long-Evans; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D018698:Glutamic Acid; D009271:Naltrexone; C045444:U 69593