title: Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors.
abstract: Understanding the neurobiological bases for sex differences in alcohol dependence is needed to help guide the development of individualized therapies for alcohol abuse disorders. In the present study, alcohol-induced adaptations in (1) anxiety-like behavior, (2) patterns of c-Fos activation and (3) subcellular distribution of corticotropin releasing factor receptor in locus coeruleus (LC) neurons was investigated in male and female Sprague-Dawley rats that were chronically exposed to ethanol using a liquid diet. Results confirm and extend reports by others showing that chronic ethanol exposure produces an anxiogenic-like response in both male and female subjects. Ethanol-induced sex differences were observed with increased c-Fos expression in LC neurons of female ethanol-treated subjects compared to controls or male subjects. Results also reveal sex differences in the subcellular distribution of the CRFr in LC-noradrenergic neurons with female subjects exposed to ethanol exhibiting a higher frequency of plasmalemmal CRFrs. These adaptations have implications for LC neuronal activity and its neural targets across the sexes. Considering the important role of the LC in ethanol-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis, the present results indicate important sex differences in feed-forward regulation of the HPA axis that may render alcohol dependent females more vulnerable to subsequent stress exposure.
authors.affiliation: Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, United States. Electronic address: tara.retson@jefferson.edu.
authors.forename: T A
authors.initials: TA
authors.lastname: Retson
authors.affiliation: Department of Pharmacology and Physiology, Drexel University, Philadelphia, PA 19102, United States.
authors.forename: B A
authors.initials: BA
authors.lastname: Reyes
authors.affiliation: Department of Pharmacology and Physiology, Drexel University, Philadelphia, PA 19102, United States.
authors.forename: E J
authors.initials: EJ
authors.lastname: Van Bockstaele
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D011187:Posture; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000648:ultrastructure; D012727:Sex Characteristics; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D016760:Proto-Oncogene Proteins c-fos; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol
keywords: CRFr; Chronic alcohol; Locus coeruleus; Sex differences; c-Fos