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  • Title: Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the α-2 adrenoreceptor antagonist yohimbine.
    Author: Simms JA, Richards JK, Mill D, Kanholm I, Holgate JY, Bartlett SE.
    Journal: Psychopharmacology (Berl); 2011 Nov; 218(1):101-10. PubMed ID: 21863233.
    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.
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