title: Galanin mediates features of neural and behavioral stress resilience afforded by exercise.
abstract: Exercise promotes resilience to stress and increases galanin in the locus coeruleus (LC), but the question of whether changes in galanin signaling mediate the stress-buffering effects of exercise has never been addressed. To test the contributions of galanin to stress resilience, male Sprague Dawley rats received intracerebroventricular (ICV) cannulation for drug delivery and frontocortical cannulation for microdialysis, and were housed with or without a running wheel for 21d. Rats were acutely injected with vehicle or the galanin receptor antagonist M40 and exposed to a single session of either footshock or no stress. Other groups received galanin, the galanin receptor antagonist M40, or vehicle chronically for 21d prior to the stress session. Microdialysis sampling occurred during stress exposure and anxiety-related behavior was measured on the following day in the elevated plus maze. Dendritic spines were visualized by Golgi impregnation in medial prefrontal cortex (mPFC) pyramidal neurons and quantified. Exercise increased galanin levels in the LC. Under non-stressed conditions, anxiety-related behavior and dopamine levels were comparable between exercised and sedentary rats. In contrast, exposure to stress reduced open arm exploration in sedentary rats but not in exercise rats or those treated chronically with ICV galanin, indicating improved resilience. Both exercise and chronic, ICV galanin prevented the increased dopamine overflow and loss of dendritic spines observed after stress in sedentary rats. Chronic, but not acute M40 administration blocked the resilience-promoting effects of exercise. The results indicate that increased galanin levels promote features of resilience at both behavioral and neural levels.
authors.affiliation: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA. Electronic address: natale.sciolino@nih.gov.
authors.forename: N R
authors.initials: NR
authors.lastname: Sciolino
authors.affiliation: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA. Electronic address: jmsmith9@uga.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.affiliation: Physiology Department, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: astranahan@gru.edu.
authors.forename: A M
authors.initials: AM
authors.lastname: Stranahan
authors.affiliation: Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA. Electronic address: kgf@uga.edu.
authors.forename: K G
authors.initials: KG
authors.lastname: Freeman
authors.affiliation: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA; Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA. Electronic address: gedwards@uga.edu.
authors.forename: G L
authors.initials: GL
authors.lastname: Edwards
authors.affiliation: Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: dweinsh@emory.edu.
authors.forename: D
authors.initials: D
authors.lastname: Weinshenker
authors.affiliation: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA; Psychology Department, University of Georgia, Athens, GA 30602, USA. Electronic address: pvholmes@uga.edu.
authors.forename: P V
authors.initials: PV
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000534:rehabilitation; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D019004:Galanin / Q000008:administration & dosage / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000008:administration & dosage; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology* / Q000534:rehabilitation*
chemical_list: C079517:M40; D010446:Peptide Fragments; D019004:Galanin
keywords: Dopamine; Frontal cortex; Galanin; Locus coeruleus; Plasticity; Stress resilience