Deficit in brain reward function and acute and protracted anxiety-like behavior after discontinuation of a chronic alcohol liquid diet in rats

Abstract

RATIONALE Discontinuation of chronic and excessive alcohol consumption leads to a dysphoric state in humans. It is not known if there are changes in brain reward function after the discontinuation of an alcohol liquid in rats. OBJECTIVES The aim of these studies was to investigate the effect of withdrawal from an alcohol liquid diet on brain reward function and acute and protracted anxiety-like behavior. METHODS The intracranial self-stimulation procedure was used to assess brain reward function and the elevated plus maze test was used to assess anxiety-like behavior. RESULTS Discontinuation of chronic, 12 weeks, exposure to a 6.2% v/v alcohol liquid diet lead to a minor deficit in brain reward function and did not increase anxiety-like behavior. Discontinuation of chronic, 12 weeks, exposure to a 10% v/v alcohol liquid diet lead to a pronounced deficit in brain reward function and increased anxiety-like behavior. Two weeks after discontinuation of the 10% v/v alcohol liquid diet, the rats with a history of alcohol dependence did not display increased anxiety-like behavior. Restraint stress increased anxiety-like behavior in the rats with a history of alcohol dependence, but not in the control rats. Brain reward thresholds were assessed during the chronic 10% v/v alcohol exposure period. During this period there were no differences between the brain rewards thresholds of the alcohol and control rats. CONCLUSION These findings indicate that withdrawal from a 10% v/v alcohol liquid diet leads to a pronounced deficit in brain reward function and acute and protracted anxiety-like behavior in rats.

Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

“…Although people may not always experience the full spectrum of the physical signs of oxycodone withdrawal, they still may be inflicted with those unpleasant enough to promote escalation of self-dosing, with the drug obtained either through legitimate or illegitimate channels. ICSS has been proposed as a preclinical model that can be used to model affective-like withdrawal symptoms, because many drugs, including morphine (Schaefer and Michael, 1986;Easterling et al, 2000;Liu and Schulteis, 2004;Altarifi and Negus, 2011;Holtz et al, 2015), nicotine (Epping-Jordan et al, 1998;Cryan et al, 2003;Kenny and Markou, 2005;Igari et al, 2014;Manbeck et al, 2014;Qi et al, 2015), ethanol (Schulteis et al, 1995;Chester et al, 2006;Rylkova et al, 2009;Boutros et al, 2014), and cocaine (Markou and Koob, 1991;Stoker and Markou, 2011), produce decreases in ICSS after either spontaneous or precipitated withdrawal. Furthermore, withdrawal from nicotine and morphine has been associated with decreased ventral tegmental area dopaminergic activity, which correlates with ICSS deficits (Liu and Jin, 2004;Kaufling and Aston-Jones, 2015).…”

Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats

“…The discontinuation of ethanol vapor exposure or ethanol liquid diet administration has been reported to increase anxiety-like behavior in a variety of rodents models in multiple settings such as the EPM test (Baldwin et al 1991), the acoustic startle procedure, and the social interaction test, as recently reviewed (Rylkova et al 2009). In general, anxiety-like behavior in the EPM test during withdrawal may be observed also after single bouts of ethanol intoxication, characterizing the ADE (Zhang et al 2007).…”

“…Enhanced Bemotionality^is one of the factors considered as a putative contributor to the increased alcohol consumption (Williams et al 2012) and relapse. Repeated alcohol withdrawal sessions increase anxiety-like behaviors associated with alcohol withdrawal (Rylkova et al 2009) and potentiate the severity of alcohol withdrawal-induced seizures (Becker and Hale 1993). Withdrawal severity is generally positively correlated with BEC (Logan et al 2012), and to a certain extent, emotionality behaviors induced by alcohol withdrawal are dependent on the concentration of alcohol in the liquid diet and the amount of drug taken by the individuals (Rylkova et al 2009).…”

“…Repeated alcohol withdrawal sessions increase anxiety-like behaviors associated with alcohol withdrawal (Rylkova et al 2009) and potentiate the severity of alcohol withdrawal-induced seizures (Becker and Hale 1993). Withdrawal severity is generally positively correlated with BEC (Logan et al 2012), and to a certain extent, emotionality behaviors induced by alcohol withdrawal are dependent on the concentration of alcohol in the liquid diet and the amount of drug taken by the individuals (Rylkova et al 2009). To verify how several cycles of ethanol withdrawal/re-exposure interfere with ethanol consumption, a model of liquid meal with and without ethanol was applied.…”

“…The repeated ADE paradigm is considered a good model of dependence, including the alcohol drinking relapses and their consequences (Melendez et al 2006;Sanchis-Segura and Spanagel 2006). Alcohol liquid diets are widely used to study the neurobiological mechanisms underlying alcohol effects (Rylkova et al 2009). However, limited data are available to explain how the repeated withdrawal from a chronic moderate dose of alcohol is detrimental to the nervous system.…”