Intermittent Access to 20% Ethanol Induces High Ethanol Consumption in Long–Evans and Wistar Rats

Abstract

Background There has been some difficulty getting standard laboratory rats to voluntarily consume large amounts of ethanol without the use of initiation procedures. It has previously been shown that standard laboratory rats will voluntarily consume high levels of ethanol if given intermittent-access to 20% ethanol in a 2-bottle-choice setting [Wise, Psychopharmacologia 29 (1973), 203]. In this study, we have further characterized this drinking model. Methods Ethanol-naïve Long–Evans rats were given intermittent-access to 20% ethanol (three 24-hour sessions per week). No sucrose fading was needed and water was always available ad libitum. Ethanol consumption, preference, and long-term drinking behaviors were investigated. Furthermore, to pharmacologically validate the intermittent-access 20% ethanol drinking paradigm, the efficacy of acamprosate and naltrexone in decreasing ethanol consumption were compared with those of groups given continuous-access to 10 or 20% ethanol, respectively. Additionally, ethanol consumption was investigated in Wistar and out-bred alcohol preferring (P) rats following intermittent-access to 20% ethanol. Results The intermittent-access 20% ethanol 2-bottle-choice drinking paradigm led standard laboratory rats to escalate their ethanol intake over the first 5 to 6 drinking sessions, reaching stable baseline consumption of high amounts of ethanol (Long–Evans: 5.1 ± 0.6; Wistar: 5.8 ± 0.8 g/kg/24 h, respectively). Furthermore, the cycles of excessive drinking and abstinence led to an increase in ethanol preference and increased efficacy of both acamprosate and naltrexone in Long–Evans rats. P-rats initiate drinking at a higher level than both Long–Evans and Wistar rats using the intermittent-access 20% ethanol paradigm and showed a trend toward a further escalation in ethanol intake over time (mean ethanol intake: 6.3 ± 0.8 g/kg/24 h). Conclusion Standard laboratory rats will voluntarily consume ethanol using the intermittent-access 20% ethanol drinking paradigm without the use of any initiation procedures. This model promises to be a valuable tool in the alcohol research field.

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

“…All mice were group‐housed and maintained at a 12/12 hour light/dark cycle. Adult post pubertal age‐matched male Rcc Han Wistar rats (Harlan, Horst, Netherlands) were used as they are known to voluntarily consume alcohol using the intermittent access model and thereby reach physiological relevant blood alcohol concentrations (Simms et al., 2008). They were housed individually in high Macrolon III cages covered with filter tops (Tecniplast, Varese, Italy) and maintained on a 12‐hour reversed light dark cycle.…”

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

“…Fluid intake was measured 30 min after the bottle exchange on each ethanol drinking day. The intermittent drinking paradigm has previously been shown to produce relatively high levels of ethanol intake in male Long-Evans rats (Wise, 1973;Simms et al, 2008). Furthermore, this drinking paradigm has been shown to engender elevated ethanol intake in SI compared with GH rats (Chappell et al, 2013;Skelly et al, 2015).…”

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

“…We also showed that chlorzoxazone, an FDA-approved SK activator used for decades as a centrally acting myorelaxant, significantly reduces excessive alcohol intake in rats with intermittent access to ethanol, but does not reduce the more moderate alcohol intake in rats with continuous access to alcohol (Hopf et al, 2011). Alcohol intake in intermittent-access rats shows a number of other features, which have been considered to perhaps model some aspects of human alcoholism, including escalation of intake, sensitivity to compounds that reduce alcohol intake in human alcoholics (Steensland et al, 2007; Novel therapeutic strategies for addiction G Addolorato et al ............................................................................................................................................................... Simms et al, 2008;McKee et al, 2009) and aversion-resistant and perhaps compulsive alcohol intake (Hopf et al, 2010b). Thus, the SK activator chlorzoxazone may represent a potent and immediately accessible treatment for human alcoholism.…”