Your browser doesn't support javascript.
loading
Inhibition of norepinephrine signaling during a sensitive period disrupts locus coeruleus circuitry and emotional behaviors in adulthood.
Meng, Qingyuan; Garcia-Garcia, Alvaro L; Dranovsky, Alex; Leonardo, E David.
Affiliation
  • Meng Q; Dranovsky-Leonardo Lab (ADL Lab), Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Dr. Box 87, New York, NY, 10032, USA.
  • Garcia-Garcia AL; Dranovsky-Leonardo Lab (ADL Lab), Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Dr. Box 87, New York, NY, 10032, USA.
  • Dranovsky A; Dranovsky-Leonardo Lab (ADL Lab), Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Dr. Box 87, New York, NY, 10032, USA. ad722@cumc.columbia.edu.
  • Leonardo ED; Dranovsky-Leonardo Lab (ADL Lab), Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Dr. Box 87, New York, NY, 10032, USA. el367@cumc.columbia.edu.
Sci Rep ; 13(1): 3077, 2023 02 22.
Article in En | MEDLINE | ID: mdl-36813805
Deficits in arousal and stress responsiveness are a feature of numerous psychiatric disorders including depression and anxiety. Arousal is supported by norepinephrine (NE) released from specialized brainstem nuclei, including the locus coeruleus (LC) neurons into cortical and limbic areas. During development, the NE system matures in concert with increased exploration of the animal's environment. While several psychiatric medications target the NE system, the possibility that its modulation during discreet developmental periods can have long-lasting consequences has not yet been explored. We used a chemogenetic strategy in mice to reversibly inhibit NE signaling during brief developmental periods and then evaluated any long-lasting impact of our intervention on adult NE circuit function and on emotional behavior. We also tested whether developmental exposure to the α2 receptor agonist guanfacine, which is commonly used in the pediatric population and is not contraindicated during pregnancy and nursing, recapitulates the effect seen with the chemogenetic strategy. Our results reveal that postnatal days 10-21 constitute a sensitive period during which alterations in NE signaling lead to changes in baseline anxiety, increased anhedonia, and passive coping behaviors in adulthood. Disruption of NE signaling during this sensitive period also caused altered LC autoreceptor function, along with circuit specific changes in LC-NE target regions at baseline, and in response to stress. Our findings indicate an early critical role for NE in sculpting brain circuits that support adult emotional function. Interfering with this role by guanfacine and similar clinically used drugs can have lasting implications for mental health.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Locus Coeruleus / Norepinephrine Type of study: Diagnostic_studies Limits: Animals / Child / Humans Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Locus Coeruleus / Norepinephrine Type of study: Diagnostic_studies Limits: Animals / Child / Humans Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Country of publication: