A stimulus-control account of regulated drug intake in rats.

Leigh V Panlilio, Eric B Thorndike, Charles W Schindler
Author Information
  1. Leigh V Panlilio: National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov

Abstract

RATIONALE: Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not.
OBJECTIVE: This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement.
MATERIALS AND METHODS: Rats' nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments.
RESULTS: Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration.
CONCLUSION: This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing.

References

  1. Pharmacol Biochem Behav. 2000 Jan 1;65(1):83-9 [PMID: 10638640]
  2. J Exp Anal Behav. 2003 Jan;79(1):111-35 [PMID: 12696744]
  3. Psychopharmacology (Berl). 1999 Oct;146(3):303-12 [PMID: 10541731]
  4. Science. 1998 Oct 9;282(5387):298-300 [PMID: 9765157]
  5. Psychopharmacology (Berl). 1998 Jun;137(3):253-8 [PMID: 9683003]
  6. Ann N Y Acad Sci. 2006 Aug;1074:497-504 [PMID: 17105948]
  7. Nat Neurosci. 2001 Sep;4(9):943-7 [PMID: 11528427]
  8. J Exp Anal Behav. 2000 Mar;73(2):211-24 [PMID: 10784010]
  9. Psychopharmacology (Berl). 2005 Jul;180(3):436-46 [PMID: 15726333]
  10. Exp Clin Psychopharmacol. 2001 May;9(2):131-43 [PMID: 11518086]
  11. Psychopharmacology (Berl). 2003 Apr;167(1):9-19 [PMID: 12644888]
  12. Psychopharmacology (Berl). 1996 Jun;125(3):202-8 [PMID: 8815954]
  13. Brain Res. 1999 Aug 21;839(1):85-93 [PMID: 10482802]
  14. Pharmacol Biochem Behav. 1977 Nov;7(5):459-61 [PMID: 563601]
  15. Psychopharmacologia. 1974 Jan 14;34(3):255-64 [PMID: 4819978]
  16. J Exp Psychol Anim Behav Process. 1992 Jul;18(3):236-50 [PMID: 1619392]
  17. Psychopharmacology (Berl). 1998 Mar;136(1):70-4 [PMID: 9537684]
  18. Behav Pharmacol. 1991 Nov;2(4 And 5):283-286 [PMID: 11224071]
  19. Pharmacol Biochem Behav. 2006 Jun;84(2):235-43 [PMID: 16814853]
  20. Pharmacol Biochem Behav. 1999 Oct;64(2):337-45 [PMID: 10515310]
  21. Psychopharmacology (Berl). 2005 Jul;180(3):473-90 [PMID: 15731896]
  22. Psychopharmacology (Berl). 2000 May;150(1):61-6 [PMID: 10867977]
  23. J Neurosci. 1999 May 15;19(10):4102-9 [PMID: 10234038]
  24. Pharmacology. 2007;80(2-3):65-119 [PMID: 17570954]
  25. J Pharmacol Exp Ther. 1968 May;161(1):122-9 [PMID: 5648489]
  26. J Exp Anal Behav. 1974 Sep;22(2):381-90 [PMID: 16811801]
  27. J Pharmacol Exp Ther. 2002 May;301(2):698-704 [PMID: 11961075]

Grants

  1. Z01 DA000001-23/Intramural NIH HHS
  2. Z99 DA999999/Intramural NIH HHS

MeSH Term

Analgesics, Opioid
Animals
Cocaine
Conditioning, Operant
Cues
Discrimination Learning
Dopamine Uptake Inhibitors
Dose-Response Relationship, Drug
Light
Male
Piperidines
Rats
Rats, Sprague-Dawley
Remifentanil
Reward
Self Administration

Chemicals

Analgesics, Opioid
Dopamine Uptake Inhibitors
Piperidines
Cocaine
Remifentanil

Word Cloud

Created with Highcharts 10.0.0drugself-administrationlevelstimulusreinforcingreinforcementwilllighthighlyregularself-injectionmightadditionaleffectThuscontrolemulatedusingschedulefoodproducedaccountregulatedintakeratsRATIONALE:PatternsoftenconsistentpausepausingoccuranimallearnedinjectionsreachedcertainpossiblyduesystemreachingfullcapacityinteroceptiveeffectsfunctiondiscriminativesignalingnotOBJECTIVE:hypotheticalaspectMATERIALSANDMETHODS:Rats'nose-pokeresponsescuepresentadministeredtimeHoweverstatedeterminedcalculatingwhole-bodyresponsesessioninjectionpresentedvirtualspecificthresholdrangedosescocaineremifentanilparametersbasedpreviousexperimentsRESULTS:Responsepatternsdose-dependentremarkablysimilaractualCONCLUSION:similaritysuggestsemulationmayprovidereasonablemodelcontingenciesinherentresultssupportlearndiscriminatefallenpointanotherstimulus-control

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