Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression.
While epidemiological studies show that alcohol abuse is often co-morbid with affective disorders, the causal direction of this association is unclear. We examined this relationship using mouse models including social defeat stress (SDS), social interaction (SI) and voluntary alcohol consumption. C57BL6/J mice exposed to SDS segregate into two subpopulations, those that express depressive-like phenotypes ('susceptible') and those that do not ('resilient'). First, we stratified SDS-exposed mice and measured their voluntary alcohol consumption. Next, we determined whether SI behavior in alcohol-naïve mice could predict alcohol intake. Finally, we assessed the effect of binge-like alcohol exposure on sensitivity to SDS. We quantified Tacr1 (neurokinin-1 receptor gene) and Avp (vasopressin peptide gene) mRNA in brain regions involved in depression, addiction and social behavior. We found that susceptible mice consumed more alcohol compared with resilient mice, suggesting that depression-like phenotypes associate with increased alcohol intake. Interestingly, we observed a negative correlation between SI and alcohol intake in stress- and alcohol-naïve mice, suggesting that individual differences in SI associate with alcohol preference. Finally, alcohol pre-treatment increased sensitivity to SDS, indicating that alcohol exposure alters sensitivity to social stress. Quantification of mRNA revealed that increased expression of Tacr1 and Avp generally associated with decreased SI and increased alcohol intake. C57BL6/J mice are an inbred strain; thus, it is likely that individual differences in behavior and gene expression are driven by epigenetic factors. Collectively, these results support a bidirectional relationship between alcohol exposure and susceptibility to stress that is associated with variations in neuropeptide expression.
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, GA, USA.
Britta S
BS
Nelson
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, GA, USA.
Michelle K
MK
Sequeira
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, GA, USA.
Jesse R
JR
Schank
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics* / Q000378:metabolism; D055500:Resilience, Psychological; D012919:Social Behavior; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D001127:Arginine Vasopressin
Alcohol; amygdala; neurokinin-1 receptor; nucleus accumbens; stress; vasopressin