Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording.
1. Intracellular recordings were made from presumed dopamine-containing neurones in the ventral tegmental area (VTA) in rat brain slices. 2. Nicotine (10-100 microM) and acetylcholine (ACh) depolarized the neurones. The depolarization caused by ACh was typically biphasic; both components were increased by neostigmine (0.1-10 microM), but only the slower component was blocked by scopolamine (1-10 microM). 3. The nicotinic action of ACh, studied in the presence of neostigmine and scopolamine, persisted in the presence of tetrodotoxin (1 microM) and cobalt (2-5 mM). 4. ACh or carbachol (30 microM) caused inward currents in neurones voltage-clamped near the resting potential. These currents reversed polarity at around -4 mV, were blocked by hexamethonium (1-100 microM) in a voltage-dependent manner, and showed desensitization with prolonged or repeated agonist applications. 5. Depolarizations caused by ACh and carbachol were reduced in slices pretreated with kappa-bungarotoxin, but were not changed by alpha-bungarotoxin. 6. These responses to ACh and nicotine resemble those previously described on autonomic ganglion cells. The direct action on VTA neurones may contribute to the positive reinforcement associated with nicotine consumption.
Calabresi
P
P
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Lacey
M G
MG
North
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004594:Electrophysiology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology*
D002038:Bungarotoxins; D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; D009538:Nicotine; D002217:Carbachol; D000109:Acetylcholine