Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression

Danai Riga, Leanne J.M. Schmitz, Yvar van Mourik, Witte J.G. Hoogendijk, Taco J. De Vries, August B. Smit, Sabine Spijker

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat–induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, heightened motivation to acquire alcohol, persistent alcohol seeking despite alcohol unavailability, signs of extinction resistance, and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol seeking and alcohol taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

Original languageEnglish
JournalAddiction Biology
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Cite this

Riga, D., Schmitz, L. J. M., van Mourik, Y., Hoogendijk, W. J. G., De Vries, T. J., Smit, A. B., & Spijker, S. (Accepted/In press). Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression. Addiction Biology. https://doi.org/10.1111/adb.12701
Riga, Danai ; Schmitz, Leanne J.M. ; van Mourik, Yvar ; Hoogendijk, Witte J.G. ; De Vries, Taco J. ; Smit, August B. ; Spijker, Sabine. / Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression. In: Addiction Biology. 2018.
@article{2263f436960e4282b77f83010d8fdb6b,
title = "Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression",
abstract = "Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat–induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, heightened motivation to acquire alcohol, persistent alcohol seeking despite alcohol unavailability, signs of extinction resistance, and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol seeking and alcohol taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.",
keywords = "comorbidity, depression resilience, depression susceptibility",
author = "Danai Riga and Schmitz, {Leanne J.M.} and {van Mourik}, Yvar and Hoogendijk, {Witte J.G.} and {De Vries}, {Taco J.} and Smit, {August B.} and Sabine Spijker",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/adb.12701",
language = "English",
journal = "Addiction Biology",
issn = "1355-6215",
publisher = "Wiley-Blackwell",

}

Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression. / Riga, Danai; Schmitz, Leanne J.M.; van Mourik, Yvar; Hoogendijk, Witte J.G.; De Vries, Taco J.; Smit, August B.; Spijker, Sabine.

In: Addiction Biology, 01.01.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Stress vulnerability promotes an alcohol-prone phenotype in a preclinical model of sustained depression

AU - Riga, Danai

AU - Schmitz, Leanne J.M.

AU - van Mourik, Yvar

AU - Hoogendijk, Witte J.G.

AU - De Vries, Taco J.

AU - Smit, August B.

AU - Spijker, Sabine

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat–induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, heightened motivation to acquire alcohol, persistent alcohol seeking despite alcohol unavailability, signs of extinction resistance, and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol seeking and alcohol taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

AB - Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat–induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, heightened motivation to acquire alcohol, persistent alcohol seeking despite alcohol unavailability, signs of extinction resistance, and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol seeking and alcohol taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

KW - comorbidity

KW - depression resilience

KW - depression susceptibility

UR - http://www.scopus.com/inward/record.url?scp=85058695187&partnerID=8YFLogxK

U2 - 10.1111/adb.12701

DO - 10.1111/adb.12701

M3 - Article

JO - Addiction Biology

JF - Addiction Biology

SN - 1355-6215

ER -