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

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Abstract

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.

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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.

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Author notes

  1. Stephen P. Arneric

    Present address: Pharmacia Corporation, CNS Discovery Research, 7245-25-180, 7000 Portage Road, Kalamazoo, MI 49007, USA

  2. Mark A. Smith

    Present address: Global Experimental Medicine, AstraZeneca, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850-5437, USA

Authors and Affiliations

  1. Alzheimer's Research Center, Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA

    John N. Bain & Jerry J. Buccafusco

  2. Medical Research Service, Department of Veterans Affairs Medical Center, Augusta, GA 30904, USA

    Alvin V. Terry Jr & Jerry J. Buccafusco

  3. University of Georgia College of Pharmacy, Clinical Pharmacy Program, Medical College of Georgia, Augusta, GA 30912, USA

    Alvin V. Terry Jr

  4. Department of Psychology, University of Kentucky, Lexington, KY 40546, USA

    Mark A. Prendergast

  5. DuPont Pharmaceuticals Company, CNS Research, Wilmington, DE 19880-0400, USA

    Stephen P. Arneric & Mark A. Smith

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  1. John N. Bain
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Corresponding author

Correspondence to Jerry J. Buccafusco.

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Bain, J.N., Prendergast, M.A., Terry, A.V. et al. Enhanced attention in rhesus monkeys as a common factor for the cognitive effects of drugs with abuse potential. Psychopharmacology 169, 150–160 (2003). https://doi.org/10.1007/s00213-003-1483-1

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  • DOI: https://doi.org/10.1007/s00213-003-1483-1

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