Expression and function of striatal nAChRs differ in the Flinders sensitive (FSL) and resistant (FRL) rat lines

Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by nicotine. In the present study, we measured dopamine (DA) content in striatal dialysates to investigate the sensitivity of FSL and FRL r...

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Published in:Neuropharmacology 2000-10, Vol.39 (13), p.2624-2631
Main Authors: Auta, J, Lecca, D, Nelson, M, Guidotti, A, Overstreet, D.H, Costa, E, Javaid, J.I
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chromatography, High Pressure Liquid
Dopamine
Dopamine - analysis
Dopamine - metabolism
Flinders Lines rats
In vivo microdialysis
Indicators and Reagents
Male
Mecamylamine
Medical sciences
Microdialysis
Neostriatum - metabolism
Nicotine
Nicotine - pharmacology
Nicotinic acetylcholine
Nicotinic Agonists - pharmacology
Radioligand Assay
Rats
Rats, Inbred Strains
Receptors
Receptors, Nicotinic - biosynthesis
Receptors, Nicotinic - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
RNA, Messenger - biosynthesis
Tobacco, tobacco smoking
Toxicology
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Summary:Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by nicotine. In the present study, we measured dopamine (DA) content in striatal dialysates to investigate the sensitivity of FSL and FRL rats to nicotine delivered locally through a microdialysis probe placed in the striatum. We also measured the expression density of striatal high-affinity nicotinic acetylcholine receptors (nAChRs), and that of mRNAs encoding for α3, α4, α7 and β2 nAChR subunits in both lines. The DA content of dialysates was measured before and after a 1-min perfusion of nicotine (6, 10 or 20 nmoles/min) and the resulting DA increase was taken as a measure of the alkaloid's intrinsic activity for nAChRs involved in the release of DA. The nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of nicotine, suggesting that the intrinsic activity of nicotine was greater in the FSL than in the FRL rats. This was further supported by our finding that the density of high-affinity nAChRs in the striatum of FSL rats was 44% greater than in the FRL rats, whereas affinity ( K D) was virtually the same in the two lines of rats. Also the expression of mRNAs encoding for α 4, α 7, and β 2 subunits in the striatum was greater in FSL than in FRL rats (attomol/μg total RNA, α 4:98±10 vs 77±7; α 7:279±16 vs 184±16; β 2:310±19 vs 201±12). We hypothesize that the difference in nicotine-induced DA release in the striatum of FSL and FRL rats depends on the difference in nAChR subunit expression in the striatum between the two lines. The Flinders rats could be used as a model for nicotine self-administration studies to evaluate the susceptibilities of FSL and FRL rats to nicotine dependence.
ISSN:0028-3908
1873-7064
DOI:10.1016/S0028-3908(00)00082-4