Different nicotinic acetylcholine receptor subtypes mediating striatal and prefrontal cortical [3H]dopamine release.
Different nicotinic acetylcholine receptor subtypes appear to modulate dopamine release from the striatum and prefrontal cortex. In this study a combination of subtype-selective antagonists and agonists were used to extensively characterize the nAChRs involved in dopamine release from slice preparations of these two brain regions. alpha-conotoxin-MII inhibited nicotine-evoked [3H]dopamine (DA) release from striatum by 45%, but did not affect cortical dopamine release. Neither methyllycaconitine, alpha-bungarotoxin, nor alpha-conotoxin-ImI affected nicotine-evoked [3H]DA release from either striatum or prefrontal cortex. MG 624, a novel selective nAChR antagonist, inhibited cortical [3H]DA by 53%, but had no effect on striatal release. Compared to nicotine, (+/-)-UB-165 showed less efficacy with respect to dopamine release from striatum, and had no effect on cortical dopamine release. (+/-)-UB-165-evoked striatal dopamine release was completely blocked by mecamylamine, partially blocked (up to 55%) by alpha-conotoxin-MII, and unaffected by methyllycaconitine or alpha-conotoxin-ImI. alpha4beta2* and alpha6beta2beta3* nAChRs appear to play a role in striatal dopamine release, whereas alpha4beta2* nAChRs modulate release from prefrontal cortex. alpha7* nAChRs do not appear to play a role in nAChR-mediated dopamine release from either brain region.
Cao
Ying-Jun
YJ
Neurological Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA.
Surowy
Carol S
CS
Puttfarcken
Pamela S
PS
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000145:classification / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
C407663:(2-chloro-5-pyridyl)-9-azabicyclo(4.2.1)non-2-ene; D001952:Bridged-Ring Compounds; D002038:Bungarotoxins; D020916:Conotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; D011978:Receptors, Nicotinic; D013267:Stilbenes; D014316:Tritium; C087686:alpha-conotoxin ImI; C118602:triethyl-(beta-4-stilbenoxyethyl)ammonium; D009538:Nicotine; D004298:Dopamine