The effects of nicotine on dopamine and DOPAC output from rat striatal tissue.
The effects of varying doses of nicotine infusion upon spontaneous (basal) and subsequent potassium chloride-stimulated dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) output from superfused corpus striatal tissue fragments of male rats were tested. Spontaneous dopamine and DOPAC outputs were increased in response to 1, 5 and 10, but not to 0.1 and 0 (control) microM concentrations of nicotine. Interestingly, the subsequent K+-stimulated (30 mM) dopamine output was completely abolished in preparations infused with the 5 and 10 microM nicotine, but not with the 1 or 0.1 microM nicotine. No overall significant differences in K+-stimulated DOPAC were obtained among the five doses. In experiment 2, the effects of an initial infusion of amphetamine (10 microM), potassium chloride (30 mM), nicotine (10 microM) or normal superfusion medium (control) were compared upon subsequent K+-evoked dopamine release. The amount of dopamine released in response to the second (subsequent) infusion of K+ was significantly greater in the potassium chloride and control conditions versus the nicotine and amphetamine stimulated groups. No overall differences in DOPAC output were observed among the four conditions of experiment 2. These results demonstrate that nicotine can exert differential modulatory effects upon striatal dopaminergic activity as a function of the dose. The augmented levels of DOPAC output along with the abolition of the K+-stimulated dopamine release in response to the 5 and 10 microM nicotine doses suggest that these doses may simultaneously produce an activation of intraneuronal metabolism of dopamine to DOPAC along with an activation of release and inhibition of uptake to diminish stores available for subsequent responses to K+ stimulation.
Dluzen
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Department of Anatomy, College of Medicine, Northeastern Ohio Universities, Rootstown 44272-0095, USA. ded@neoucom.edu
Anderson
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D005731:Ganglionic Stimulants; D015102:3,4-Dihydroxyphenylacetic Acid; D011189:Potassium Chloride; D009538:Nicotine; D000661:Amphetamine; D004298:Dopamine