Relapse (Number of Detoxifications) in Abstinent Male Alcohol-Dependent Patients as Related to Personality Traits and Types of Tolerance to Frustration

Baars, M. Y.; Müller, Matthias; Gallhofer, Bernd; Netter, Petra

doi:10.1159/000350483

Cited by 26 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to violence, high emotional reactivity during sustained abstinence may be a large contributing factor to relapse, in heavy binge-drinking adolescents (Winward et al 2014). Relapse was most highly correlated with aggression, more so than with impulsivity, anxiety, and depression in abstinent male alcoholics (Baars et al 2013). We report that high proportions of mice show aggression during withdrawal from 8 wks EtOH.…”

Section: Discussionmentioning

confidence: 99%

“…Features of EtOH withdrawal can include dysfunctional social and aggressive behavior (Broadwater et al 2011; Overstreet et al 2002; Varlinskaya and Spear 2004), in addition to common symptoms such as headaches, fever, convulsions, and anxiety (Trevisan et al 1998). Experimental studies examining either recovering alcoholics or heavy, binge-drinking youths independently link greater increases in frustration and irritability during early abstinence to a higher chance of relapse (Baars et al 2013; Winward et al 2014). It would be beneficial to identify a translational model of EtOH withdrawal-induced aggression.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

et al. 2015

View full text Add to dashboard Cite

Rationale Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. Objectives The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH, and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Methods Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20% EtOH. Aggressive and non-aggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. Results At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression, and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5 mg/kg dose in mice with a history of 8 weeks EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks EtOH compared to 1 week EtOH or 8 weeks water. Five mg/kg memantine increased glutamate in 8 week EtOH mice, but also in 1 week EtOH and water drinkers. Conclusions These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Aggression is a common behavioral correlate of ethanol withdrawal in rodents (e.g., Hwa et al, 2015) and the present findings are consistent with this given that aggression was the most prominent withdrawal symptom observed, though other common motor abnormalities were observed. Baars et al (2013) have reported that aggression is highly correlated with mood disorders and risk of relapse in a sample of male alcohol-dependent patients. The present findings also demonstrated that ORG 34517 attenuated increases in CORT plasma levels during the third withdrawal period from the chronic, intermittent intoxication regimen.…”

Section: Discussionmentioning

confidence: 99%

Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic–pituitary–adrenal axis activation

Reynolds

Saunders

Brewton

et al. 2015

Drug and Alcohol Dependence

View full text Add to dashboard Cite

Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence.

show abstract

“…Although minimally studied empirically to assess effects on substance use, frustration is one common type of stressor frequently reported to occasion problematic drinking in humans (Baars, Müller, Gallhofer, & Netter, 2013;Miller, 1991). Operationally, frustrations are events during which previous contingencies cease to produce expected reinforcement (Amsel, 1958;Skinner, 1950).…”

mentioning

confidence: 99%

Effects of negative incentive shifts in food reward on rats' consumption of concurrent ethanol solutions

Sawyer

Galuska

Cutright

et al. 2019

J Exper Analysis Behavior

View full text Add to dashboard Cite

Frustration stress, typically operationalized as the unexpected loss of reinforcement, has been shown to engender substance use. Abrupt reductions in reinforcer magnitude likely also function as frustration stressors. These negative incentive shifts were previously shown to produce tap-and sweetened-water drinking in rats. The purpose of this study was to investigate whether these shifts in food reward would occasion oral ethanol self-administration. Nine male Long-Evans rats operated on a two-component multiple fixed-ratio schedule with signaled components producing either a large (4 pellets) or small (1pellet) reinforcer. Components were pseudorandomly arranged to present 4 transitions between past and upcoming reinforcer magnitudes: small-to-large, small-to-small, large-to-large, and large-to-small (negative incentive shift). Experiment 1 investigated the effects of negative incentive shifts on consumption of concurrent, freely available 10% sucrose, 10% sucrose plus 10% ethanol, and following sucrose fading, 10% ethanol. Experiment 2 entailed continuation of schedule contingencies with a dose manipulation of 4 ethanol concentrations (0, 5, 10, and 20%) to assess dose-dependent differences in transition-type control and consumption. A lever-press extinction condition was then conducted with 10% ethanol availability. In this novel model of frustration stress, negative incentive shifts prompted ethanol self-administration at each dose investigated, whereas the other transitions did not.

show abstract

Relapse (Number of Detoxifications) in Abstinent Male Alcohol-Dependent Patients as Related to Personality Traits and Types of Tolerance to Frustration

Cited by 26 publications

References 40 publications

Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic–pituitary–adrenal axis activation

Effects of negative incentive shifts in food reward on rats' consumption of concurrent ethanol solutions

Contact Info

Product

Resources

About