Hierarchical cue control of cocaine seeking in the face of cost

Val Collins, Kaisa N. Bornhoft, Amy Wolff, Sonal Sinha, Benjamin T. Saunders

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Rationale: Addiction is characterized by intermittent drug seeking despite rising costs. This behavior is heavily influenced by environmental stimuli that signal drug availability and reinforce drug seeking. Objective: To establish the relationship between three key aspects of human drug use in rats: the intermittent, binge nature of drug intake, the motivational conflict of drug seeking in the face of escalating negative costs, and the ability of different drug cues to interact to modulate relapse. Methods: Male and female rats were trained to self-administer cocaine on an intermittent access schedule, where brief drug-availability states were signaled by a shift in the ambient lighting of the environment, and cocaine infusions were signaled by a separate proximal discrete cue. Rats then went through a conflict procedure, where foot shock intensity associated with cocaine seeking was escalated until intake was suppressed. We then completed relapse tests where the drug-delivery cue was noncontingently presented alone, or in the context of dynamic drug-availability state transitions. Results: Intermittent access spurred psychomotor sensitization and binge-like cocaine intake. The intensity of binge-like drug taking during training was predictive of later drug seeking despite escalating costs during conflict. In relapse tests, the ability of a proximal discrete drug cue to trigger relapse was gated by the presence of a global cue signaling drug-availability state transitions. Conclusions: Our results suggest that the pattern of drug intake plays a role in many features of addiction, including modifying an individual’s willingness to endure high costs associated with drug seeking. Furthermore, our studies indicate that drug-related sensory information can be hierarchically organized to exert a dynamic modulating influence on drug-seeking motivation.

Original languageEnglish (US)
Pages (from-to)461-476
Number of pages16
JournalPsychopharmacology
Volume240
Issue number3
DOIs
StatePublished - Mar 2023

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants T32-DA007234, F32-DA051138, and R00-DA042895 .

Publisher Copyright:
© 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Keywords

  • Addiction
  • Cocaine
  • Conflict
  • Footshock
  • Individual differences
  • Intermittent access
  • Rat
  • Relapse

PubMed: MeSH publication types

  • Journal Article

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