Long-term potentiation of excitatory inputs to brain reward areas by nicotine.
Nicotine reinforces smoking behavior by activating nicotinic acetylcholine receptors (nAChRs) in the midbrain dopaminergic (DA) reward centers, including the ventral tegmental area (VTA). Although nicotine induces prolonged excitation of the VTA in vivo, the nAChRs on the DA neurons desensitize in seconds. Here, we show that activation of nAChRs on presynaptic terminals in the VTA enhances glutamatergic inputs to DA neurons. Under conditions where the released glutamate can activate NMDA receptors, long-term potentiation (LTP) of the excitatory inputs is induced. Both the short- and the long-term effects of nicotine required activation of presynaptic alpha7 subunit-containing nAChRs. These results can explain the long-term excitation of brain reward areas induced by a brief nicotine exposure. They also show that nicotine alters synaptic function through mechanisms that are linked to learning and memory.
Mansvelder
H D
HD
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637, USA.
McGehee
D S
DS
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D009538:Nicotine; D004298:Dopamine