Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine.
The effect of intravenous (i.v.) nicotine on the single unit activity of midbrain dopamine (DA) neurons was studied in rats under either local or general anesthesia. Nicotine (50-500 micrograms/kg) produced a dose-related increase in the firing rate of nigral pars compacta DA cells (A9), up to 25% above baseline, irrespective of the preparation. The same range of doses was more than three times as effective on ventral tegmental area DA cells (A10) in rats paralyzed and given a local anesthetic. By contrast, the majority of these cells were temporarily depressed in deeply anesthetized animals. All of the above effects were reversed and prevented by i.v. mecamylamine suggesting the involvement of nicotine cholinergic receptors. Moreover, after nicotine-induced stimulation, low doses of i.v. apomorphine inhibited the firing rate similar to controls indicating that dopamine receptors are not directly involved in the nicotinic action. The results suggest that acute nicotine shares with other drugs of abuse the characteristic of being more effective in stimulating A10 than A9 neurons.
Mereu
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Department of Pharmacology, St. Louis University School of Medicine, MO 63104.
Yoon
K W
KW
Boi
V
V
Gessa
G L
GL
Naes
L
L
Westfall
T C
TC
D000200:Action Potentials / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
D008464:Mecamylamine; D009538:Nicotine; D001058:Apomorphine; D004298:Dopamine