Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.
Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats with a strong sexual dimorphism. The potential impact of these alterations in early adulthood remains to be elucidated.
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Francisco Javier
FJ
Pavón
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
Eva María
EM
Marco
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Mariam
M
Vázquez
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Laura
L
Sánchez
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Patricia
P
Rivera
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Ana
A
Gavito
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
Virginia
V
Mela
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Francisco
F
Alén
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Juan
J
Decara
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Juan
J
Suárez
Departamento de Biología Celular, Facultad de Psicología, Universidad Complutense, Madrid, Spain.
Elena
E
Giné
Departamento de Biología Celular, Facultad de Psicología, Universidad Complutense, Madrid, Spain.
José Antonio
JA
López-Moreno
Servicio de Pediatría y Endocrinología Pediátrica, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa (IP), Madrid, Spain.|Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn) Instituto de Salud Carlos III, Madrid, Spain.
Julie
J
Chowen
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Fernando
F
Rodríguez-de-Fonseca
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Antonia
A
Serrano
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
María Paz
MP
Viveros
Prog Lipid Res. 2016 Apr;62:107-28
26965148
Pharmacol Ther. 2011 Dec;132(3):215-41
21798285
J Immunol. 2005 Jan 1;174(1):456-63
15611271
Genes Brain Behav. 2007 Feb;6(1):1-18
17233637
Cell Metab. 2008 Mar;7(3):227-35
18316028
Biol Psychiatry. 2009 Apr 15;65(8):662-70
19095222
Nat Rev Immunol. 2002 Mar;2(3):205-9
11913071
Behav Genet. 2012 Jan;42(1):40-56
21818662
Biol Sex Differ. 2015 Dec 12;6:33
26693004
Alcohol Clin Exp Res. 2012 Jun;36(6):984-94
22141465
Drug Alcohol Depend. 2013 Dec 1;133(2):789-93
24060590
Hepatology. 2011 Jan;53(1):346-55
21254182
J Stud Alcohol. 2004 Mar;65(2):204-12
15151351
Nature. 1993 Sep 2;365(6441):61-5
7689702
J Exp Med. 1997 Aug 29;186(5):631-43
9271579
Nat Rev Immunol. 2005 Aug;5(8):606-16
16056254
Alcohol Res Health. 2002;26(4):257-63
12875035
Behav Brain Res. 2015;287:163-71
25827923
J Psychopharmacol. 2012 Jan;26(1):164-76
21669929
Glia. 2003 Jan 15;41(2):161-8
12509806
Life Sci. 2013 Mar 19;92(8-9):476-81
22728714
Alcohol. 2008 Jun;42(4):237-47
18411007
Hepatology. 2011 Oct;54(4):1217-26
21735467
Glia. 2005 Nov 1;52(2):163-8
15920730
Int J Mol Sci. 2016 Mar 29;17 (4):472
27043532
Br J Pharmacol. 2012 Apr;165(7):2274-91
21951309
Alcohol Clin Exp Res. 2007 May;31(5):855-67
17386072
Toxicol Pathol. 2006;34(5):455-65
17067939
Alcohol Clin Exp Res. 2003 Nov;27(11):1838-45
14634502
Addict Biol. 2013 Nov;18(6):955-69
24283982
Alcohol Clin Exp Res. 2008 Dec;32(12):2149-60
18828796
J Immunol. 2011 Dec 1;187(11):5720-32
22048769
Eur J Pharmacol. 2015 Aug 15;761:28-35
25934566
J Neuroimmune Pharmacol. 2010 Mar;5(1):83-91
20020329
Addict Biol. 2016 May 22;:null
27212249
Int J Drug Policy. 2015 Feb;26(2):131-4
25107830
Addict Biol. 2016 Jul;21(4):859-72
26037332
J Neuroimmune Pharmacol. 2016 Dec;11(4):669-679
27287619
Can J Biochem Physiol. 1959 Aug;37(8):911-7
13671378
Lupus. 1999;8(5):380-3
10455517
J Neurochem. 1999 Feb;72 (2):522-8
9930723
Mol Pharmacol. 1998 Apr;53(4):676-83
9547358
J Neuroimmune Pharmacol. 2013 Jun;8(3):608-20
23471521
Toxicol Appl Pharmacol. 1993 Nov;123(1):16-25
8236255
Alcohol. 2004 Aug;34(1):35-8
15670663
Eur J Biochem. 1995 Aug 15;232(1):54-61
7556170
Addict Behav. 2008 Feb;33(2):225-34
17997047
Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
10817843
Front Behav Neurosci. 2011 Sep 28;5:64
21991251
Alcohol Alcohol. 1999 Nov-Dec;34(6):830-41
10659718
Addict Biol. 2015 Jul;20(4):756-72
24854157
Cytometry B Clin Cytom. 2004 Sep;61(1):35-9
15351980
J Leukoc Biol. 2003 Oct;74(4):486-96
12960289
J Biol Chem. 1996 May 31;271(22):13175-83
8662742
Trends Neurosci. 1990 Oct;13(10):420-3
1700516
Glia. 2010 Jan 15;58(2):135-47
19565660
Alcohol Clin Exp Res. 2010 Sep 1;34(9):1489-511
20586763