Conditioned stimuli affect ethanol-seeking by female alcohol-preferring (P) rats: the role of repeated-deprivations, cue-pretreatment, and cue-temporal intervals
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.
KeywordsDrug-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.
- Ferri M, Amato L, Davoli M (2006) Alcoholics Anonymous and other 12-step programmes for alcohol dependence. Cochrane Database Syst Rev (3):CD005032Google Scholar
- Hauser SR, Deehan GA Jr, Knight CP, Toalston JE, McBride WJ, Rodd ZA (2016) Parameters of context-induced ethanol (EtOH)-seeking in alcohol-preferring (P) rats: temporal analysis, effects of repeated deprivation, and EtOH priming injections. Alcohol Clin Exp Res 40:2229–2239CrossRefPubMedPubMedCentralGoogle Scholar
- Hilbrom ME (1990) Alcohol withdrawal seizures and binge versus chronic drinking. In: Port RJ, Mattson RH, Cramer JA, Diamond I (eds) Alcohol and seizures: basic mechanisms and clinical concepts. FA Davis, Philadelphia, pp 206–215Google Scholar
- Honig WK, Staddon JER (1977) Handbook of operant behavior. Prentice-Hall, Englewood CliffsGoogle Scholar
- McClernon FJ, Conklin CA, Kozink RV, Adcock RA, Sweitzer MM, Addicott MA, Chou YH, Chen NK, Hallyburton MB, DeVito AM (2016) Hippocampal and insular response to smoking-related environments: neuroimaging evidence for drug-context effects in nicotine dependence. Neuropsychopharmacology 41:877–885CrossRefPubMedGoogle Scholar
- Research Institute for Laboratory Animal Research (2011) Guide for the care and use of laboratory animals, 8th edn. The National Academies Press, Washington, D.CGoogle Scholar
- Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li T-K, Lumeng L, McBride WJ (2005a) Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther 315:648–657CrossRefPubMedPubMedCentralGoogle Scholar
- Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ (2005b) Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res 29:358–366CrossRefPubMedGoogle Scholar
- Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li T-K (2002a) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure. Alcohol Clin Exp Res 26:1632–1641CrossRefPubMedGoogle Scholar
- Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li T-K (2002b) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: II. Adult exposure. Alcohol Clin Exp Res 26:1642–1652CrossRefPubMedGoogle Scholar