Locomotor stimulant effects of nornicotine: Role of dopamine

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

doi:10.1016/S0091-3057(02)00960-7

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 journal › Article › peer-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 language	English
Pages (from-to)	87-94
Number of pages	8
Journal	Pharmacology Biochemistry and Behavior
Volume	74
Issue number	1
DOIs	https://doi.org/10.1016/S0091-3057(02)00960-7
State	Published - 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.

Funders	Funder 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 Abuse	F31DA006093
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 Service	DA08656, DA00399
U.S. Public Health Service
University of Kentucky	F31 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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10.1016/S0091-3057(02)00960-7

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title = "Locomotor stimulant effects of nornicotine: Role of dopamine",

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.",

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author = "Green, \{T. A.\} and Brown, \{R. W.\} and Phillips, \{S. B.\} and Dwoskin, \{L. P.\} and Bardo, \{M. T.\}",

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.",

year = "2002",

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doi = "10.1016/S0091-3057(02)00960-7",

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T2 - Role of dopamine

AU - Green, T. A.

AU - Brown, R. W.

AU - Phillips, S. B.

AU - Dwoskin, L. P.

AU - Bardo, M. T.

N1 - 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.

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Y1 - 2002/12

N2 - 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.

AB - 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.

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KW - Metabolism

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KW - Synthesis

KW - Tobacco alkaloid

KW - Tolerance

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Locomotor stimulant effects of nornicotine: Role of dopamine

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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