Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats.
Abstract
L-Nicotine stimulates locomotor activity in rats which have had prior experience of the drug. The present study investigated whether this behavioral effect is related to activation of the mesolimbic dopamine system. In the first experiment, l-nicotine (0.2-0.8 mg/kg s.c.) stimulated locomotor activity and increased dopamine utilization in the olfactory tubercle, as judged by the ratio of the concentration of dihydroxyphenylacetic acid to dopamine. In other experiments, l-nicotine (0.1-0.4 mg/kg) stimulated locomotor activity in a dose-related, stereoselective manner; after pretreatment with the l-aromatic amino acid decarboxylase inhibitor NSD-1015, l-nicotine increased 3,4-dihydroxyphenylalanine/dopamine ratios in olfactory tubercle and nucleus accumbens, suggesting increased dopamine utilization, although absolute concentrations of 3,4-dihydroxyphenylalanine and dopamine were in general not significantly altered. This neurochemical action of l-nicotine was dose-dependent, stereoselective and absent in the caudate-putamen at the doses tested. l-Nicotine did not alter indices of 5-hydroxytryptamine utilization. The locomotor stimulant effect of l-nicotine was abolished by bilateral intra-accumbens microinjection of 6-hydroxydopamine, which depleted markedly mesolimbic terminal areas of dopamine. Thus, in rats which have been chronically treated with l-nicotine, a selective activation of mesolimbic dopamine appears to mediate the locomotor stimulant effect of this drug.
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Lesions of the VTA and its primary projection area, the NAc, greatly attenuate nicotine self-administration and the psychostimulant properties of nicotine.
“Lesions of the ventral tegmental area (VTA) and its primary projection area, the nucleus accumbens (NAc), greatly attenuate nicotine self-administration and the psychostimulant properties of nicotine”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Clarke et al. 1988
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“Given that the mesolimbic dopamine system has been shown to underlie the locomotor stimulant action of nicotine (Clarke et al. 1988), and that dopamine neurons within the mesolimbic system are more sensitive to nicotine-induced long term potentiation during adolescence than adulthood (Placzek et…”
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- Authors
- Clarke, P. B., Fu, D. S., Jakubovic, A., & Fibiger, H. C.
- Affiliations
- University of British Columbia (CA)
- ORCID
- Clarke, P B
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1988-08
- Volume
- 246
- Issue
- 2
- Pages
- 701-708
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2226370386
- Cited by
- 318
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- locomotor stimulation, mesolimbic dopamine system, olfactory tubercle, nucleus accumbens, dopamine utilization, stereoselectivity, NSD-1015, 6-hydroxydopamine, caudate-putamen, nicotine tolerance
- MeSH terms
- Animals, Brain Chemistry, Dihydroxyphenylalanine, Dopamine, Injections, Subcutaneous, Limbic System, Male, Motor Activity, Nicotine, Serotonin, Stereoisomerism, 3,4-Dihydroxyphenylacetic Acid, Rats
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