title: Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.
abstract: Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.
authors.affiliation: Abbott Healthcare Products B.V. (formerly Solvay Pharmaceuticals B.V.), C.J. van Houtenlaan 36, 1381 CP, Weesp, The Netherlands.|Maynooth University Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: W
authors.initials: W
authors.lastname: Goutier
authors.affiliation: Maynooth University Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: J P
authors.initials: JP
authors.lastname: Lowry
authors.affiliation: Abbott Healthcare Products B.V. (formerly Solvay Pharmaceuticals B.V.), C.J. van Houtenlaan 36, 1381 CP, Weesp, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: McCreary
authors.affiliation: Maynooth University Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland. john.oconnor@ucd.ie.|UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland. john.oconnor@ucd.ie.
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Connor
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D008024:Ligands; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D009538:Nicotine; D004298:Dopamine
keywords: Dopamine D1 receptor; Dopamine release; Fast cyclic voltammetry; Nicotine; SCH-23390; SKF-38393