Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long–Evans rats by the α-2 adrenoreceptor antagonist yohimbine

Abstract

Rationale Developing models to efficiently explore the mechanisms by which stress can mediate reinstatement of drug-seeking behavior is crucial to the development of new pharmacotherapies for alcohol use disorders. Objectives We examined the effects of multiple reinstatement sessions using the pharmacological stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a more efficient model of stress-induced reinstatement. Methods Long–Evans rats were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20% ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self-administration sessions, followed by extinction training. After reaching extinction criteria, the animals were tested once per week with yohimbine vehicle and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions or blood collection. Levels of reinstatement and plasma corticosterone (CORT) were determined each week for four consecutive weeks. Results Yohimbine induced reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks. Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol group after the first reinstatement session but remained stable for the 20% ethanol group trained without sucrose. Plasma CORT levels in response to injection of both vehicle and yohimbine were significantly higher in the ethanol-trained animals compared to sucrose controls. Conclusions The stable reinstatement in the 20% ethanol group supports the use of this training procedure in studies using within-subject designs with multiple yohimbine reinstatement test sessions. Additionally, these results indicate that the hormonal response to stressors can be altered following extinction from self-administration of relatively modest amounts of ethanol.

Adolescent Alcohol Exposure Reduces Behavioral Flexibility, Promotes Disinhibition, and Increases Resistance to Extinction of Ethanol Self-Administration in Adulthood

“…Beginning on PD65 rats were trained to orally self-administer ethanol by first exposing them to an intermittent two-bottle choice drinking initiation paradigm for a period of two weeks (Simms et al , 2010; Simms et al , 2011). Three days per week, two bottles --- one containing water and the other containing 20% ethanol --- were placed on the cage.…”

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

“…The most commonly reported concentrations are 5 and 10% sucrose. We chose 5% over 10% based on Srisontiyakul's study, to allow comparisons with our previous publications showing that long-term consumption of 5% sucrose using the IA2BC model alters nucleus accumbens morphology and our studies showing the 5% concentration can be used to test novel compounds for their ability to reduce bingelike sucrose consumption (Steensland et al, 2010;Patkar et al, 2017;Nielsen et al, 2008;Shariff et al, 2016;Simms, Haass-Koffler, BitoOnon, Li, & Bartlett, 2012;Simms et al, 2011;Srinivasan et al, 2012).…”

Novel Cues Reinstate Cocaine-Seeking Behavior and Induce Fos Protein Expression as Effectively as Conditioned Cues

“…Stress is known to facilitate both drug reinforcement and incentive motivation, where various stressors have the ability to reinstate drug and sucrose-seeking behavior (Bossert et al, 2005;Shaham et al, 2003;Simms et al, 2011). Novel stimuli have the tendency to induce both approach and avoidance in animals, and it is the balance between these two conflicting motivations that drive subsequent behavior (Montgomery and Monkman, 1955).…”