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.
|Number of pages||8|
|Journal||Pharmacology Biochemistry and Behavior|
|State||Published - Dec 2002|
Bibliographical noteFunding 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.
- Nicotine metabolite
- Tobacco alkaloid
ASJC Scopus subject areas
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience