, Volume 236, Issue 9, pp 2835–2846 | Cite as

Conditioned stimuli affect ethanol-seeking by female alcohol-preferring (P) rats: the role of repeated-deprivations, cue-pretreatment, and cue-temporal intervals

  • Sheketha R. HauserEmail author
  • Gerald A. DeehanJr
  • Christopher P. Knight
  • Robert A. Waeiss
  • William A. Truitt
  • Philip L. Johnson
  • Richard L. Bell
  • William J. McBride
  • Zachary A. Rodd
Original Investigation



Evidence indicates that drug-paired stimuli can evoke drug-craving leading to drug-seeking and repeated relapse periods can influence drug-seeking behaviors.


The present study examined (1) the effect of an interaction between repeated deprivation cycles and excitatory conditioning stimuli (CS+) on ethanol (EtOH)-seeking; (2) the effects of EtOH-paired cue-exposure in a non-drug-paired environment on subsequent conditioning in a drug-paired environment; and (3) the temporal effects of conditioned cues on subsequent EtOH-seeking.


Adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS− associated with the absence of EtOH (extinction training), and a neutral stimulus (CS0) presented in a neutral non-drug-paired environment. The rats underwent four deprivation cycles or were non-deprived, following extinction they were maintained in a home cage for an EtOH-free period, and then exposed to no cue, CS+, CS−, or CS0 to assess the effect of the conditioned cues on EtOH-seeking behavior.


Repeated deprivations enhanced and prolonged the duration of CS+ effects on EtOH-seeking. Presentation of the CS− in a non-drug-paired environment blocked the ability of a CS+ to enhance EtOH-seeking in a drug-paired environment. Presentation of the CS+ or CS− in a non-drug-paired environment 2 or 4 h earlier significantly altered EtOH-seeking.


Results indicated an interaction between repeated deprivation cycles and CS+ resulted in a potentiation of CS+ evoked EtOH-seeking. In addition, a CS− may have therapeutic potential by providing prophylactic protection against relapse behavior in the presence of cues in the drug-using environment.


Drug-seeking Drug-craving Drug relapse Drug deprivation Alcohol relapse Alcohol-preferring (P) rats 



The work was supported in part by NIAAA grants AA07611, AA07462, AA020908, AA022287, and AA024612.

Compliance with ethical standards

All research protocols were approved by the institutional animal care and use committee and are in accordance with the guidelines of the Institutional Care and Use Committee of the National Institute on Drug Abuse, National Institutes of Health, and the Guide for the Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflict of interest.


The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIAAA or NIH.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sheketha R. Hauser
    • 1
    Email author
  • Gerald A. DeehanJr
    • 2
  • Christopher P. Knight
    • 1
  • Robert A. Waeiss
    • 3
  • William A. Truitt
    • 4
  • Philip L. Johnson
    • 4
  • Richard L. Bell
    • 1
  • William J. McBride
    • 1
  • Zachary A. Rodd
    • 1
  1. 1.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of PsychologyEast Tennessee State UniversityJohnson CityUSA
  3. 3.Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research InstituteIndianapolisUSA
  4. 4.Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisUSA

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