Long-term potentiation of excitatory inputs to brain reward areas by nicotine

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.