Enhanced attention in rhesus monkeys as a common factor for the cognitive effects of drugs with abuse potential

John N. Bain, Mark A. Prendergast, Alvin V. Terry, Stephen P. Arneric, Mark A. Smith, Jerry J. Buccafusco

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Rationale: One of the common neurochemical features of many drugs of abuse is their ability to directly or indirectly enhance dopaminergic activity in the brain, particularly within the ventral tegmental-nucleus accumbens pathway. Dopaminergic pathways in the frontal and limbic cortex also may be targets for these agents, where pharmacological effects could result in heightened attention and/or support self-administration behavior. Objectives: The purpose of this study was to determine whether drugs from differing pharmacological classes that exhibit abuse potential would share the ability to counter distractability in the delayed matching task. Methods: Well trained mature macaques performed a computer-assisted delayed matching-to-sample task which included trials associated with three delay intervals and randomly interspersed task-relevant distractors. Drug regimens included four to five doses and subjects were tested no more than twice per week. Results: All but one of the six compounds (tomoxetine), on average, increased task accuracy for either non-distractor or distractor trials. It was evident that for several compounds, doses required to improve accuracy for non-distractor trials were routinely greater than the doses required to improve accuracy for distractor trials. Data for the individualized Best dose (based upon the subject's optimal level of accuracy during distractor trials) revealed statistically significant distractor-related improvements in task accuracy for the same five compounds. The relative efficacy for reversing distractor-induced decrements in task accuracy was estimated by the level of improvement with respect to baseline: nomifensine (31%)>nicotine (22%)≈morphine (19%)≈caffeine (19%)≈methylphenidate (22%) >tomoxetine (9%). Tomoxetine (noradrenergic preferring) was the only compound that did not produce a significant improvement in accuracy. Conclusions: These results provide pharmacological support for the concept that attentional mechanisms may play an important role in the "environmental" associative aspects of drug seeking behavior, and as such they may provide the basis for treatment strategies aimed at preventing relapse in detoxified addicts.

Original languageEnglish
Pages (from-to)150-160
Number of pages11
Issue number2
StatePublished - Sep 2003

Bibliographical note

Funding Information:
Acknowledgements This work was supported in part by the DuPont Pharmaceuticals Company, the Alzheimer’s Association, and by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. The authors also wish to acknowledge the excellent technical assistance provided by Ms. Nancy Kille.


  • Attention
  • Delayed matching
  • Dopamine agonist
  • Drug abuse
  • Monkey
  • Operant task

ASJC Scopus subject areas

  • Pharmacology


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