Psychopharmacology

, Volume 170, Issue 4, pp 409–422 | Cite as

Apparatus bias and place conditioning with ethanol in mice

  • Christopher L. Cunningham
  • Nikole K. Ferree
  • MacKenzie A. Howard
Original Investigation

Abstract

Rationale

Although the distinction between "biased" and "unbiased" is generally recognized as an important methodological issue in place conditioning, previous studies have not adequately addressed the distinction between a biased/unbiased apparatus and a biased/unbiased stimulus assignment procedure. Moreover, a review of the recent literature indicates that many reports (70% of 76 papers published in 2001) fail to provide adequate information about apparatus bias. This issue is important because the mechanisms underlying a drug's effect in the place-conditioning procedure may differ depending on whether the apparatus is biased or unbiased.

Objectives

The present studies were designed to assess the impact of apparatus bias and stimulus assignment procedure on ethanol-induced place conditioning in mice (DBA/2 J). A secondary goal was to compare various dependent variables commonly used to index conditioned place preference.

Methods

Apparatus bias was manipulated by varying the combination of tactile (floor) cues available during preference tests. Experiment 1 used an unbiased apparatus in which the stimulus alternatives were equally preferred during a pre-test as indicated by the group average. Experiment 2 used a biased apparatus in which one of the stimuli was strongly preferred by most mice (mean % time on cue = 67%) during the pre-test. In both studies, the stimulus paired with drug (CS+) was assigned randomly (i.e., an "unbiased" stimulus assignment procedure). Experimental mice received four pairings of CS+ with ethanol (2 g/kg, i.p.) and four pairings of the alternative stimulus (CS−) with saline; control mice received saline on both types of trial. Each experiment concluded with a 60-min choice test.

Results

With the unbiased apparatus (experiment 1), significant place conditioning was obtained regardless of whether drug was paired with the subject's initially preferred or non-preferred stimulus. However, with the biased apparatus (experiment 2), place conditioning was apparent only when ethanol was paired with the initially non-preferred cue, and not when it was paired with the initially preferred cue. These conclusions held regardless of which dependent variable was used to index place conditioning, but only if the counterbalancing factor was included in statistical analyses.

Conclusions

These studies indicate that apparatus bias plays a major role in determining whether biased assignment of an ethanol-paired stimulus affects ability to demonstrate conditioned place preference. Ethanol's ability to produce conditioned place preference in an unbiased apparatus, regardless of the direction of the initial cue bias, supports previous studies that interpret such findings as evidence of a primary rewarding drug effect. Moreover, these studies suggest that the asymmetrical outcome observed in the biased apparatus is most likely due to a measurement problem (e.g., ceiling effect) rather than to an interaction between the drug's effect and an unconditioned motivational response (e.g., "anxiety") to the initially non-preferred stimulus. More generally, these findings illustrate the importance of providing clear information on apparatus bias in all place-conditioning studies.

Keywords

Conditioned place preference Place conditioning Biased apparatus Unbiased apparatus Biased procedure Unbiased procedure Ethanol Inbred mice DBA/2J 

Notes

Acknowledgements

This research was supported by NIAAA grants AA07702 and AA07468. Thanks are extended to Carly Petersen for assistance in data analysis and to Anita Bechtholt and Rick Bevins for comments and suggestions. We also thank Rachel Smith for help in constructing floors.

References

  1. Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology 153:31–43Google Scholar
  2. Blander A, Hunt T, Blair R, Amit Z (1984) Conditioned place preference: an evaluation of morphine's positive reinforcing properties. Psychopharmacology 84:124–127PubMedGoogle Scholar
  3. Bozarth MA (1987) Conditioned place preference: a parametric analysis using systemic heroin injections. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 241–273Google Scholar
  4. Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Liebman JM, Cooper SJ (eds) Neuropharmacological basis of reward. Oxford, New York, pp 264–319Google Scholar
  5. Cervo L, Rossi C, Samanin R (1993) Clonidine-induced place preference is mediated by alpha 2-adrenoceptors outside the locus coeruleus. Eur J Pharmacol 238:201–207CrossRefPubMedGoogle Scholar
  6. Cunningham CL (1993) Pavlovian drug conditioning. In: van Haaren F (ed) Methods in behavioral pharmacology. Elsevier, Amsterdam, pp 349–381Google Scholar
  7. Cunningham CL (1995) Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice. Psychopharmacology 120:28–41PubMedGoogle Scholar
  8. Cunningham CL, Prather LK (1992) Conditioning trial duration affects ethanol-induced conditioned place preference in mice. Anim Learn Behav 20:187–194Google Scholar
  9. Cunningham CL, Niehus DR, Malott DH, Prather LK (1992) Genetic differences in the rewarding and activating effects of morphine and ethanol. Psychopharmacology 107:385–393PubMedGoogle Scholar
  10. Cunningham CL, Dickinson SD, Okorn DM (1995) Naloxone facilitates extinction but does not affect acquisition or expression of ethanol-induced conditioned place preference. Exp Clin Psychopharmacol 3:330–343Google Scholar
  11. Cunningham CL, Okorn DM, Howard CE (1997) Interstimulus interval determines whether ethanol produces conditioned place preference or aversion in mice. Anim Learn Behav 25:31–42Google Scholar
  12. Cunningham CL, Henderson CM, Bormann NM (1998) Extinction of ethanol-induced conditioned place preference and conditioned place aversion: effects of naloxone. Psychopharmacology 139:62–70PubMedGoogle Scholar
  13. Cunningham CL, Tull LE, Rindal KE, Meyer PJ (2002) Distal and proximal pre-exposure to ethanol in the place-conditioning task: tolerance to aversive effect, sensitization to activating effect, but no change in rewarding effect. Psychopharmacology 160:414–424CrossRefPubMedGoogle Scholar
  14. Heinrichs SC, Martinez JL (1986) Modification of place preference conditioning in mice by systemically administered [leu]enkephalin. Behav Brain Res 22:249–255CrossRefPubMedGoogle Scholar
  15. Hinson RE, Wall A-M, Swayze IG (1991) Place avoidance conditioning with d-amphetamine: the effect of screening and the use of preferred and non-preferred sides. J Psychopharmacol 5:207–214Google Scholar
  16. Nomikos GG, Spyraki C (1988) Cocaine-induced place conditioning: importance of route of administration and other procedural variables. Psychopharmacology 94:119–125Google Scholar
  17. Rescorla RA, Wagner AR (1972) A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Black AH, Prokasy WF (eds) Classical conditioning II: current research and theory. Appleton-Century-Crofts, New York, pp 64–99Google Scholar
  18. Schechter MD (1995) Cocaethylene produces conditioned place preference in rats. Pharmacol Biochem Behav 51:549–552CrossRefPubMedGoogle Scholar
  19. Schenk S, Ellison F, Hunt T, Amit Z (1985) An examination of heroin conditioning in preferred and nonpreferred environments and in differentially housed mature and immature rats. Pharmacol Biochem Behav 22:215–220CrossRefPubMedGoogle Scholar
  20. Spyraki C, Kazandijan A, Varonos D (1985) Diazepam-induced place preference conditioning: appetitive and antiaversive properties. Psychopharmacology 87:225–232Google Scholar
  21. Swerdlow NR, Gilbert D, Koob GF (1989) Conditioned drug effects on spatial preference: critical evaluation. In: Boulton AA, Baker GB, Greenshaw AJ (eds) Psychopharmacology (Neuromethods, vol 13). Humana Press, Clifton, pp 399–446Google Scholar
  22. Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Progr Neurobiol 56:613–672CrossRefGoogle Scholar
  23. van der Kooy D (1987) Place conditioning: a simple and effective method for assessing the motivational properties of drugs. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 229–240Google Scholar
  24. Vezina P, Stewart J (1987a) Conditioned locomotion and place preference elicited by tactile cues paired exclusively with morphine in an open field. Psychopharmacology 91:375–380Google Scholar
  25. Vezina P, Stewart J (1987b) Morphine conditioned place preference and locomotion: the effect of confinement during training. Psychopharmacology 93:257–260PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Christopher L. Cunningham
    • 1
  • Nikole K. Ferree
    • 1
  • MacKenzie A. Howard
    • 1
  1. 1.Department of Behavioral Neuroscience and Portland Alcohol Research CenterOregon Health and Science UniversityPortlandUSA

Personalised recommendations