Nicotine reinforces smoking behavior by activating nicotinic acetylcholine
receptors (nAChRs) in the mid-brain dopaminergic (DA) reward centers, inclu
ding 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 i
n the VTA enhances glutamatergic inputs to DA neurons. Under conditions whe
re the released glutamate can activate NMDA receptors, long-term potentiati
on (LTP) of the excitatory inputs is induced. Both the short- and the long-
term effects of nicotine required activation of presynaptic alpha 7 subunit
-containing nAChRs. These results can explain the long-term excitation of b
rain reward areas induced by a brief nicotine exposure. They also show that
nicotine alters synaptic function through mechanisms that are linked to le
arning and memory.