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

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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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Acknowledgements

We would like to thank Rui Li, Haley Pierson, and Tiffany Ho for excellent technical assistance. This work was supported by funding from the State of California for Medical Research through UCSF to S.E.B., Department of Defense Grant W81XWH-06-0240 and W81XWH-10-1-0247 to S.E.B. The experiments contained herein comply with the current laws of the USA. All procedures were pre-approved by the Gallo Center Institutional Animal Care and Use Committee and were in accordance with NIH guidelines for the Humane Care and Use of Laboratory Animals. This work was supported by funding the NIH, 1RO1AA017924-01 to S.E.B.

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Authors and Affiliations

  1. Preclinical Development Group, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA, 94608, USA

    Jeffrey A. Simms, Jemma K. Richards, Douglas Mill, Isabel Kanholm, Joan Y. Holgate & Selena E. Bartlett

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  1. Jeffrey A. Simms
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  2. Jemma K. Richards
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  3. Douglas Mill
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  4. Isabel Kanholm
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  5. Joan Y. Holgate
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  6. Selena E. Bartlett
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Correspondence to Selena E. Bartlett.

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Simms, J.A., Richards, J.K., Mill, D. et al. Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long–Evans rats by the α-2 adrenoreceptor antagonist yohimbine. Psychopharmacology 218, 101–110 (2011). https://doi.org/10.1007/s00213-011-2451-9

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