title: Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.
abstract: Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression-alcoholism relationship still deserves further investigation.
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain. Electronic address: emmarco@bio.ucm.es.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Marco
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Javier Antonio
authors.initials: JA
authors.lastname: Ballesta
authors.affiliation: Departamento de Fisiología Humana, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Irala
authors.affiliation: Departamento de Fisiología Humana, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María-Donina
authors.initials: MD
authors.lastname: Hernández
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Serrano
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Mela
authors.affiliation: Departamento de Fisiología Humana, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: López-Gallardo
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain. Electronic address: pazviver@bio.ucm.es.
authors.forename: María-Paz
authors.initials: MP
authors.lastname: Viveros
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology*; D059445:Anhedonia; D000818:Animals; D001835:Body Weight; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004435:Eating; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D046353:Immobility Response, Tonic; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C507071:NCAM140, rat; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D016708:Synaptophysin
keywords: Alcohol; Animal models; Cannabinoid receptors; Depression; Frontal cortex; GFAP; Hippocampus; Sex differences; Synaptic plasticity; Two-bottle choice