title: The effects of nicotine and tobacco particulate matter on dopamine uptake in the rat brain.
abstract: Cigarette smoking is the leading cause of preventable death worldwide. Recently, tobacco extracts have been shown to have a different pharmacological profile to nicotine alone and there is increasing evidence of a role for non-nicotinic components of cigarette smoke in smoking addiction. Nicotine is known to affect the uptake of dopamine in the brain of laboratory animals, but studies in the literature are often contradictory and little is known of the effects on non-nicotinic tobacco components on dopamine uptake. This study has examined the acute and chronic effects of nicotine and a tobacco extract (TPM) on dopamine uptake by the dopamine and norepinephrine transporters (DAT and NET) ex vivo using rotating disk electrode voltammetry, and quantified DAT and NET protein and mRNA expression in key brain regions. Nicotine (0.35 mg/kg) significantly decreased DAT function in the nucleus accumbens (NAc) at 30 min with no change in protein expression. This effect was sensitive to mecamylamine and DHβE but not MLA, indicating that it is dependent on α4 subunit containing nicotinic receptors. Furthermore, TPM, but not nicotine, increased DAT function in the dorsal striatum at 1 h in a nicotinic receptor independent manner with no change in DAT protein expression. At 1 h DAT mRNA in the ventral tegmental area was decreased by both acute and chronic TPM treatments.
authors.affiliation: School of Biological Sciences, Centre for Biodiscovery, Department of Science, Victoria University of Wellington, Wellington, 6140, New Zealand.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Danielson
authors.forename: Fraser
authors.initials: F
authors.lastname: Putt
authors.forename: Penelope
authors.initials: P
authors.lastname: Truman
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: Kivell
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D014028:Tobacco Smoke Pollution; D014026:Nicotiana
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018733:Nicotinic Antagonists; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine; D000157:Aconitine
keywords: addiction; dopamine transporter; norepinephrine transporter