The frequency-dependence of the nicotine-induced inhibition of dopamine is controlled by the α7 nicotinic receptor.
Voltammetric analyses show that low (100-500 nM) doses of nicotine regulate striatal dopamine by inhibiting release evoked by a single stimulation to a greater extent than release evoked by high frequency stimulations. This frequency-dependent inhibition is because of nicotine desensitizing heteromeric β2 subunit-containing nicotinic acetylcholine receptor (nAChR) subtypes. Surprisingly, a high dose of nicotine (2 μM; capable of interacting with additional nAChR subtypes) produced an inhibition of dopamine evoked by high frequency stimulation, an effect that was not seen with the low dose of nicotine or the β2 antagonist, dihydro-β-erythroidine hydrobromide. This inhibition was replicated by application of α7 nAChR antagonists methyllcaconitine citrate or α-bungarotoxin in conjunction with the low dose of nicotine or dihydro-β-erythroidine hydrobromide. Blocking α7 receptor function alone produced a modest increase in dopamine evoked by single pulse stimulation while not affecting dopamine evoked by high frequency stimulation. The antagonist results were mimicked using selective α7 agonists PHA 543613 and PNU 282987. The frequency dependence of the low dose nicotine inhibition therefore requires functional α7 nAChRs, and may arise from differing levels of endogenous acetylcholine evoked by the stimulation.
Seipel
Andrew T
AT
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Yakel
Jerrel L
JL
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D004298:Dopamine; D018691:Excitatory Amino Acid Antagonists; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat