Sex-dependent Associations Between Addiction-related Behaviors and the Microbiome in Outbred Rats

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2020 May 14

PMID 32403084

Citations 28

Authors

Veronica L Peterson

Jerry B Richards

Paul J Meyer

Raul Cabrera-Rubio

Jordan A Tripi

Christopher P King

Oksana Polesskaya

Amelie Baud

Apurva S Chitre

Thomaz F S Bastiaanssen

Leah Solberg Woods

Fiona Crispie

Timothy G Dinan

Paul D Cotter

Abraham A Palmer

John F Cryan

Affiliations

Soon will be listed here.

Abstract

Background: Multiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype.

Methods: Outbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype.

Results: Overall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae.

Conclusions: These data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.

Citing Articles

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References

Baud A, Mulligan M, Casale F, Ingels J, Bohl C, Callebert J . Genetic Variation in the Social Environment Contributes to Health and Disease. PLoS Genet. 2017; 13(1):e1006498. PMC: 5266220. DOI: 10.1371/journal.pgen.1006498. View

Gancarz A, San George M, Ashrafioun L, Richards J . Locomotor activity in a novel environment predicts both responding for a visual stimulus and self-administration of a low dose of methamphetamine in rats. Behav Processes. 2011; 86(2):295-304. PMC: 3045732. DOI: 10.1016/j.beproc.2010.12.013. View

Llopis M, Cassard A, Wrzosek L, Boschat L, Bruneau A, Ferrere G . Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut. 2015; 65(5):830-9. DOI: 10.1136/gutjnl-2015-310585. View

Hoban A, Stilling R, Moloney G, Moloney R, Shanahan F, Dinan T . Microbial regulation of microRNA expression in the amygdala and prefrontal cortex. Microbiome. 2017; 5(1):102. PMC: 5571609. DOI: 10.1186/s40168-017-0321-3. View

King C, Palmer A, Solberg Woods L, Hawk L, Richards J, Meyer P . Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats. Psychopharmacology (Berl). 2016; 233(13):2593-605. PMC: 5025873. DOI: 10.1007/s00213-016-4306-x. View

Klindworth A, Pruesse E, Schweer T, Peplies J, Quast C, Horn M . Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2012; 41(1):e1. PMC: 3592464. DOI: 10.1093/nar/gks808. View

Yager L, Robinson T . Individual variation in the motivational properties of a nicotine cue: sign-trackers vs. goal-trackers. Psychopharmacology (Berl). 2015; 232(17):3149-60. PMC: 4536151. DOI: 10.1007/s00213-015-3962-6. View

Bajaj J, Hylemon P, Ridlon J, Heuman D, Daita K, White M . Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012; 303(6):G675-85. PMC: 3468538. DOI: 10.1152/ajpgi.00152.2012. View

Pitchers K, Flagel S, ODonnell E, Solberg Woods L, Sarter M, Robinson T . Individual variation in the propensity to attribute incentive salience to a food cue: influence of sex. Behav Brain Res. 2014; 278:462-9. PMC: 4382370. DOI: 10.1016/j.bbr.2014.10.036. View

10.

Bravo J, Forsythe P, Chew M, Escaravage E, Savignac H, Dinan T . Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011; 108(38):16050-5. PMC: 3179073. DOI: 10.1073/pnas.1102999108. View

11.

Jaggar M, Rea K, Spichak S, Dinan T, Cryan J . You've got male: Sex and the microbiota-gut-brain axis across the lifespan. Front Neuroendocrinol. 2019; 56:100815. DOI: 10.1016/j.yfrne.2019.100815. View

12.

Collins S, Kassam Z, Bercik P . The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol. 2013; 16(3):240-5. DOI: 10.1016/j.mib.2013.06.004. View

13.

Yager L, Pitchers K, Flagel S, Robinson T . Individual variation in the motivational and neurobiological effects of an opioid cue. Neuropsychopharmacology. 2014; 40(5):1269-77. PMC: 4367472. DOI: 10.1038/npp.2014.314. View

14.

Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M . The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014; 6(263):263ra158. PMC: 4396848. DOI: 10.1126/scitranslmed.3009759. View

15.

Enoch M, Hodgkinson C, Yuan Q, Shen P, Goldman D, Roy A . The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence. Biol Psychiatry. 2009; 67(1):20-7. PMC: 2964936. DOI: 10.1016/j.biopsych.2009.08.019. View

16.

Steinway S, Biggs M, Loughran Jr T, Papin J, Albert R . Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome. PLoS Comput Biol. 2015; 11(5):e1004338. PMC: 4478025. DOI: 10.1371/journal.pcbi.1004338. View

17.

Sherwin E, Bordenstein S, Quinn J, Dinan T, Cryan J . Microbiota and the social brain. Science. 2019; 366(6465). DOI: 10.1126/science.aar2016. View

18.

Davis B, Clinton S, Akil H, Becker J . The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats. Pharmacol Biochem Behav. 2008; 90(3):331-8. PMC: 2474787. DOI: 10.1016/j.pbb.2008.03.008. View

19.

Bangsgaard Bendtsen K, Krych L, Sorensen D, Pang W, Nielsen D, Josefsen K . Gut microbiota composition is correlated to grid floor induced stress and behavior in the BALB/c mouse. PLoS One. 2012; 7(10):e46231. PMC: 3462757. DOI: 10.1371/journal.pone.0046231. View

20.

Golubeva A, Joyce S, Moloney G, Burokas A, Sherwin E, Arboleya S . Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism. EBioMedicine. 2017; 24:166-178. PMC: 5652137. DOI: 10.1016/j.ebiom.2017.09.020. View