title: β-Endorphin neuronal transplantation into the hypothalamus alters anxiety-like behaviors in prenatal alcohol-exposed rats and alcohol-non-preferring and alcohol-preferring rats.
abstract: BACKGROUND
  Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β-endorphin (β-EP)-producing neurons in the hypothalamus. In response to stress, β-EP normally provides negative feedback to the hypothalamic-pituitary-adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats.
  
  
  METHODS
  To determine whether β-EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated β-EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol-exposed, and alcohol-preferring (P) and alcohol-non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety-like behaviors in the elevated plus maze and open-field assays.
  
  
  RESULTS
  We showed that β-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol-exposed adult rats. Moreover, we showed that β-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress.
  
  
  CONCLUSIONS
  These data further establish a role of β-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol-exposed children and those genetically predisposed to increased alcohol consumption.
authors.affiliation: Endocrine Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey; University of Pittsburgh Medical Center, Department of Psychiatry, Translational Neuroscience Program, Pittsburgh, Pennsylvania.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Logan
authors.forename: Olivia
authors.initials: O
authors.lastname: Wynne
authors.forename: George
authors.initials: G
authors.lastname: Maglakelidze
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'Connell
authors.forename: Nadka I
authors.initials: NI
authors.lastname: Boyadjieva
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
mesh_terms: D000428:Alcohol Drinking / Q000628:therapy*; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000628:therapy*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D005260:Female; D008297:Male; D018782:Maze Learning; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000601:surgery*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis; D012149:Restraint, Physical; D001615:beta-Endorphin / Q000378:metabolism / Q000627:therapeutic use*; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Alcohol Drinking; Anxiety Behaviors; Beta-Endorphin Cell Therapy; Fetal Alcohol; Stress Response