Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun;40(6):1202-14.
doi: 10.1111/acer.13075. Epub 2016 May 7.

Adolescent Social Isolation as a Model of Heightened Vulnerability to Comorbid Alcoholism and Anxiety Disorders

Tracy R Butler  1 , Anushree N Karkhanis  2 , Sara R Jones  2 , Jeffrey L Weiner  2
Affiliations
Review

Adolescent Social Isolation as a Model of Heightened Vulnerability to Comorbid Alcoholism and Anxiety Disorders

Tracy R Butler et al. Alcohol Clin Exp Res. 2016 Jun.

Abstract

Individuals diagnosed with anxiety-related illnesses are at increased risk of developing alcoholism, exhibit a telescoped progression of this disease and fare worse in recovery, relative to alcoholics that do not suffer from a comorbid anxiety disorder. Similarly, preclinical evidence supports the notion that stress and anxiety represent major risk factors for the development of alcohol use disorder (AUD). Despite the importance of understanding the link between anxiety and alcoholism, much remains unknown about the neurobiological substrates underlying this relationship. One stumbling block has been the lack of animal models that reliably reproduce the spectrum of behaviors associated with increased vulnerability to these diseases. Here, we review the literature that has examined the behavioral and neurobiological outcomes of a simple rodent adolescent social isolation procedure and discuss its validity as a model of vulnerability to comorbid anxiety disorders and alcoholism. Recent studies have provided strong evidence that adolescent social isolation of male rats leads to the expression of a variety of behaviors linked with increased vulnerability to anxiety and/or AUD, including deficits in sensory gating and fear extinction, and increases in anxiety measures and ethanol drinking. Neurobiological studies are beginning to identify mesolimbic adaptations that may contribute to the behavioral phenotype engendered by this model. Some of these changes include increased excitability of ventral tegmental area dopamine neurons and pyramidal cells in the basolateral amygdala and significant alterations in baseline and stimulated catecholamine signaling. A growing body of evidence suggests that adolescent social isolation may represent a reliable rodent model of heightened vulnerability to anxiety disorders and alcoholism in male rats. These studies provide initial support for the face, construct, and predictive validity of this model and highlight its utility in identifying neurobiological adaptations associated with increased risk of developing these disorders.

Keywords: Alcohol Use Disorder; Comorbidity; Dopamine; Early Life Stress; Norepinephrine.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The diagnosis of an anxiety disorder is associated with increased risk of developing alcohol use disorder, a telescoped progression of the disease, and a poorer prognosis in recovery. One possible explanation for these deleterious associations is that antecedent anxiety may accelerate or even eliminate the transition from positive to negative reinforcement that is thought to occur during the progression from recreational drinking to the development of alcohol use disorder. Blue: positive reinforcement; Red: negative reinforcement; Bold: increase in strength of associations.
Fig. 2
Fig. 2
Summary of the effects of adolescent social isolation on catecholamine signaling in the nucleus accumbens (NAc). No baseline differences in extracellular levels of dopamine and norepinephrine were found in the NAc of socially isolated and group housed rats. However, higher dopamine transporter protein levels were observed in socially isolated accumbal tissue. Furthermore, social isolation was associated with increased electrically stimulated dopamine release and uptake (not illustrated) as well as a sensitization of both the dopaminergic and noradrenergic systems following an acute ethanol challenge.
Fig. 3
Fig. 3
Summary of the effects of adolescent social isolation on catecholamine signaling in the basolateral amygdala (BLA). Lower extracellular dopamine levels and greater dopamine transporter protein levels were observed in the BLA of socially isolated rats compared to group housed subjects. No differences in these measures were observed in the norepinephrine system across the 2 groups. However, adolescent social isolation resulted in a sensitization of the dopaminergic and noradrenergic systems in response to an acute ethanol challenge.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abel KM, Heuvelman HP, Jorgensen L, Magnusson C, Wicks S, Susser E, Hallkvist J, Dalman C. Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study. BMJ. 2014;348:f7679. - PMC - PubMed
    1. Adelman JP, Maylie J, Sah P. Small-conductance Ca2+-activated K+ channels: form and function. Annu Rev Physiol. 2012;74:245–269. - PubMed
    1. April MD, Fossum K, Hounshell C, Stolper K, Spear L, Semelrath K. A sinister cause of anterograde amnesia: painless aortic dissection. Am J Emerg Med. 2015;33:989 e985–987. - PubMed
    1. Bailey CP, O’Callaghan MJ, Croft AP, Manley SJ, Little HJ. Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption. Neuropharmacology. 2001;41:989–999. - PubMed
    1. Becker JB, Koob GF. Sex differences in animal models: focus on addiction. Pharmacol Rev. 2016;68:242–263. - PMC - PubMed

Publication types