title: Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.
abstract: Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses.
authors.affiliation: Department of Natural Sciences, State University of Southwestern Bahia, Praça Primavera, 40-Bairro Primavera, Itapetinga, BA 45700-000, Brazil; Department of Anatomy, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: elcecristina@gmail.com.
authors.forename: Elce C C
authors.initials: ECC
authors.lastname: Rebouças
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal; Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Department of Sciences, Instituto Universitário de Ciências da Saúde (IUCS), CESPU, CRL, R. Central da Gandra 1317, 4585-116 Gandra, Portugal. Electronic address: sleal@med.up.pt.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leal
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: ssilva@med.up.pt.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Silva
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: sasusana@med.up.pt.
authors.forename: Susana I
authors.initials: SI
authors.lastname: Sá
mesh_terms: D000437:Alcoholism / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Estrogen receptor; Feeding-regulatory neuropeptides; Heavy chronic ethanol treatment; Hypothalamic arcuate nucleus; Long-term withdrawal; Tyrosine hydroxylase