Locomotor stimulant effects of nornicotine: Role of dopamine

T. A. Green, R. W. Brown, S. B. Phillips, L. P. Dwoskin, M. T. Bardo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Nornicotine (NORNIC) is a tobacco alkaloid and behaviorally active nicotine metabolite in vivo. Previous behavioral research has shown that NORNIC has locomotor stimulant and reinforcing effects in rats similar to that of nicotine. Results from the current study showed that a bilateral lesion of the nucleus accumbens decreased the locomotor stimulant effect of NORNIC across repeated injections. Pretreatment with the dopamine (DA) D1 receptor antagonist SCH23390 did not block the locomotor stimulant effect of NORNIC or the initiation of sensitization following repeated NORNIC administration. The D2 receptor antagonist eticlopride, however, blocked both the stimulant effect and the initiation of sensitization following repeated NORNIC. Additionally, NORNIC was found to increase synthesis and metabolism of DA, with a greater effect in the mesolimbic pathway compared to the nigrostriatal pathway. Taken together, these results suggest that expression of NORNIC-induced locomotor activity is dependent upon ascending dopaminergic mesolimbic projections, providing additional evidence that NORNIC plays a contributory role in tobacco dependence.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume74
Issue number1
DOIs
StatePublished - Dec 2002

Bibliographical note

Funding Information:
Research was funded by USPHS grants DA00399 and DA08656. TAG supported by the Interdepartmental Neuroscience Program and the Research Challenge Trust Fund at the University of Kentucky and USPHS F31 DA06093.

Funding

Research was funded by USPHS grants DA00399 and DA08656. TAG supported by the Interdepartmental Neuroscience Program and the Research Challenge Trust Fund at the University of Kentucky and USPHS F31 DA06093.

FundersFunder number
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug AbuseF31DA006093
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse
U.S. Public Health ServiceDA08656, DA00399
U.S. Public Health Service
University of KentuckyF31 DA06093
University of Kentucky

    Keywords

    • Activity
    • Behavior
    • DOPAC
    • Locomotion
    • Metabolism
    • Nicotine metabolite
    • Sensitization
    • Synthesis
    • Tobacco alkaloid
    • Tolerance

    ASJC Scopus subject areas

    • Biochemistry
    • Toxicology
    • Pharmacology
    • Clinical Biochemistry
    • Biological Psychiatry
    • Behavioral Neuroscience

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